Total joint replacement infection control devices and methods

ABSTRACT

An orthopedic system for delivery of a therapeutic agent to a bone includes an elongate stem adapted to be inserted into an intramedullary canal, an inlet configured to receive the therapeutic agent, and one or more outlets configured to deliver the therapeutic agent to the bone. The elongate stem may comprise one or more protrusions to engage the bone, and one or more channels extending longitudinally therein, fluidly coupled to the inlet. The therapeutic agent flows from the inlet through the one or more channels and exits into the intramedullary canal through the one or more outlets. The system may be configured to allow one or more dimensions of the system to be adjusted to accommodate the anatomy of a patient.

CROSS-REFERENCE

This application claims the benefit of U.S. Provisional Application No.62/180,986, filed on Jun. 17, 2015, entitled “Total Joint ReplacementInfection Control Devices and Methods” [Attorney Docket No.44445-703.101, previously 44057-710.101], the entire contents of whichare incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

A total joint replacement (TJR) is a medical procedure that involves therepair and replacement of joints, such as hips and knees. In thesesurgical procedures, the bones at the hip or knee joints receiveorthopedic implants that mimic the structure of the joint that isreplaced.

In some cases, infection occurs and this is can be a devastatingcomplication of TJR surgeries. Unless an infection is properly diagnosedwithin the first two to four weeks following the original surgery (whichis uncommon), the infected implant must be removed in combination withan extensive debridement of the surrounding joint tissue and bone.

The current standard of care for treatment of an infected TJR in theUnited States typically involves a two-stage re-implantation process. Inthe first stage of this process, the infected components are surgicallyexposed by incision. Scar tissue is then de-bulked and other soft tissuemay be released, and sometimes an osteotomy is performed. This stagealso includes the removal of all prosthetic components and foreignmaterial including, for example, acrylic bone cement. After extensivejoint debridement of infected soft tissue and bone, a spacer blockconsisting of heavily dosed antibiotic bone cement is placed temporarilyinto the joint space. The purpose of the antibiotic bone cement is tosterilize the joint environment and to serve as an antibiotic deliverysystem. Additionally, the bone cement acts as a spacer to preserve jointspace and maintains ligament length. However, the antibiotic released bythe bone cement is uncontrolled and is quite costly to use. In addition,more operating room time is necessary to prepare this spacer material.This increases the cost of the operation

Following the removal of the infected implant and the insertion of theantibiotic bone cement spacer, the patient must generally wait betweensix and twelve weeks before the second stage of the procedure can beperformed. This period of time is necessary so that medicalprofessionals can be confident that the infection has been successfullyeradicated. Only after the infectious condition has been eliminated, maythe second stage proceed. During the second stage, the new prosthesis isre-implanted.

In other countries, such as throughout Europe, a one-stagere-implantation process has been popular. This involves the removal ofthe infected implant, as noted above, followed by aggressive debridementand then immediate re-implantation of a new implant. The success ratefor this technique has typically been lower than the two-stageprocedure. The one-state implantation process is generally reserved forpatients who are considered to be too feeble or sick to undergo thetraditional two-stage re-implantation process.

In certain situations, both one- and two-stage procedures can havedisadvantages. For example, and as noted above, the two-stagere-implantation process requires six to twelve weeks between operations.This is a very difficult time for the patient as they do not have afunctional joint in place and it is typically very painful to mobilizeor ambulate with an antibiotic spacer. Articulating spacers are somewhatbetter than static spacers, but are also more expensive as well as moredifficult and time-consuming to place during the original stage oneprocedure. From a health care standpoint, the two-stage procedure alsorequires two separate hospitalizations. Finally, from a surgeon'sstandpoint, a significant amount of scar tissue develops during the timespan between the two procedures. This makes for a very difficult andtime-consuming second stage operation. In addition, the two-stagere-implantation process involves not one, but two, very difficult andcostly surgical procedures.

On the other hand, a one-stage re-implantation surgical protocolrequires absolute identification of the infecting organism in order toproceed. Unfortunately, it is very difficult to achieve this absoluteidentification in the current health care system. In addition, aone-stage re-implantation protocol requires the use of fully-cementedcomponents. Fully-cemented components are typically not favored by U.S.surgeons for revision surgery because they require a high amount ofantibiotic which may structurally weaken the cement.

Moreover, and in both one-stage and two-stage re-implantation surgicalprotocols, the release of the antibiotic from the bone cement iscompletely uncontrolled. This is a significant disadvantage of bothprotocols and essentially acts to lengthen the time between the firstand the second surgical procedures in the two-stage re-implantationprocess.

Thus, there remains a need for a device that may be employed duringre-implantation surgical procedures that may be used to deliverantibiotic or other therapeutic agents in a controlled and titratablemanner directly into the synovial joint cavity and adjoining medullarycanals as a means of eliminating the infection following the removal ofa previous orthopedic implant. In addition, there remains a need forsuch a device that can provide stability and maintain the physicaldimensions of joint space and normal soft tissue envelope in any jointundergoing the re-implantation of an orthopedic implant. In addition,there remains a need for such a device that may be easily employed,facilitates the reduction in the time needed to conduct the stage onere-implantation surgery and that reduces the overall time between thefirst and second stages of a two-stage re-implantation surgicalprotocol. At least some of these will be addressed by the devices andmethods described herein.

2. Description of the Background Art

Other patents which disclose devices and methods for delivery of anantiobiotic to an intramedullary canal include: U.S. Pat. Nos.8,900,323; 8,900,322; and 8,454,706.

SUMMARY OF THE INVENTION

The present invention generally relates to medical systems, devices andmethods, and more particularly relates to orthopedic devices used todeliver a therapeutic agent to a joint or intramedullary canal in abone.

In one aspect of the present invention, a therapeutic agent deliverysystem comprises a first intramedullary stem configured to be disposedin a first medullary canal of a first bone, a second intramedullary stemconfigured to be disposed in a second medullary canal of a second bone,and a coupling member coupled to the first intramedullary stem and thesecond intramedullary stem. Each of the first intramedullary stem andthe second intramedullary stem comprises an elongate body having alongitudinal axis, a first end, a second end opposite the first end, anda channel extending between the first end and the second end. Each ofthe first intramedullary stem and the second intramedullary stem furthercomprises a plurality of protrusions extending radially outward from theelongate body, wherein adjacent protrusions define or more flutedregions therebetween. The plurality of protrusions are configured toengage the first medullary canal in a stable fashion, and one or moreoutlet holes are disposed in the one or more fluted regions, wherein theone or more outlet holes are in fluid communication with the channel.The coupling member may be coupled to the first end of the firstintramedullary stem and the first end of the second intramedullary stem,wherein the coupling member holds the first and second intramedullarystems together and at a fixed distance. The coupling member may furthercomprise an inlet in fluid communication with the channels in the firstand second intramedullary stems.

In some embodiments, the coupling member may comprise an adjustableheight manifold configured to increase or decrease a distance betweenthe first ends of the two intramedullary stems when the adjustableheight manifold is actuated. The adjustable height manifold may comprisea housing with a central housing channel disposed therethrough, arotating nut coupled to the housing, and an adjustable connectordisposed in the housing channel. The adjustable connector may have anadjustable connector channel disposed therein. The inlet coupled to thehousing may be fluidly connected to the adjustable connector channel,and the adjustable connector channel may be fluidly coupled with thechannel in the first stem or the second stem. Rotation of the nut canextend or retract the adjustable connector relative to the housing. Therotating nut may be threadably engaged with the adjustable connector,and the adjustable connector may be slidably disposed in the housingchannel, where rotation of the rotating nut moves the adjustableconnector up or down in the housing channel without rotation of theadjustable connector.

In some embodiments, the coupling member may comprise a wedge element,wherein disposition of the wedge element between the first end of thefirst intramedullary stem and the first end of the second medullary stemadjusts a distance between the first ends of the two intramedullarystems.

The therapeutic agent delivery system may further comprise a source ofthe therapeutic agent for delivery to the medullary canals from the oneor more outlet holes in the one or more fluted regions of the first andsecond stems. The therapeutic agent may be an antibiotic, wherein theantibiotic may comprise vancomycin, tobramycin, or a combinationthereof.

In some embodiments, the first medullary canal may be in a femur and thefirst stem may be configured to be disposed therein. The secondmedullary canal may be in a tibia and the second stem may be configuredto be disposed therein.

In some embodiments, the coupling member may be releasably coupled tothe first and second intramedullary stems.

In some embodiments, the first stem may be identical to the second stem.

In some embodiments, the first stem or the second stem may comprise fourfins equally spaced around the elongate body and extending along thelongitudinal axis thereof. The first stem or the second stem may furthercomprise a plurality of outlet holes extending axially along a linesubstantially parallel to the longitudinal axis thereof.

In some embodiments, the coupling member may comprise a flanged region,wherein the first end of the first or second stem comprises a recessedregion for receiving the flanged region, and wherein rotation of theflanged region relative to the recessed region can releasably lock thefirst end with the coupling member. One or more pins may be disposed inthe first end of the first or second stem, and the one or more pins mayprotrude therefrom thereby engaging the flanged region and preventingfurther rotation of the first or second stem relative to the couplingmember. In some embodiments, the coupling member may comprise a snap fitsection or a dovetailed section for engaging a corresponding dovetailedsection or a corresponding snap fit section on the first stem or thesecond stem.

In some embodiments, the channel may extend from the first end to thesecond end of the first or second stem, and the channel may extendthrough both the first end and the second end. The system may furthercomprise a plug disposed in the channel at the second end of the firststem or the second stem. In some embodiments, the channel may be a blindchannel in the first stem or the second stem, the blind channel having aclosed second end.

In some embodiments, the elongate body of the first stem or the secondstem may be tapered.

In some embodiments, the coupling member may comprise a housing, a firststem connector configured to engage the first end of the firstintramedullary stem, and a second stem connector configured to engagethe first end of the second intramedullary stem. The first and secondstem connectors may be disposed on opposite sides of the housing. Thefirst stem connector may have an orientation relative to the second stemconnector, wherein the orientation may remain the same during actuationof the adjustable height manifold.

In some embodiments, the coupling member may comprise a housing, whereina concave groove is disposed circumferentially around at least a portionof the housing. The concave groove may be sized to receive a tubing.

The therapeutic agent delivery system may further comprise a coverdisposed over the first stem or the second stem, or a sponge disposed inat least some of the one or more fluted regions of the first stem or thesecond stem. The cover or the sponge can be configured to facilitateeven distribution of the therapeutic agent therefrom to the first or thesecond intramedullary canal.

The therapeutic agent delivery system may further comprise a pumpconfigured to pump the therapeutic agent into the channel of the firstor the second stem.

The therapeutic agent delivery system may further comprise a vacuumpump, the vacuum pump configured to remove unwanted fluids from thefirst or the second medullary canal via the one or more outlet holes orthe channel in the first stem or the second stem.

In some embodiments, the plurality of protrusions in the first stem orthe second stem may be spirally disposed therearound, or the one or morefluted regions in the first stem or the second stem may be spirallydisposed therearound.

In some embodiments, the first stem or the second stem may have asurface area, and 50% or less of the surface area may be configured tocontact bone in the first medullary canal or the second medullary canal.

The therapeutic agent delivery system may further comprise an outletfluidly coupled to the first stem, the second stem, or the couplingmember.

In another aspect of the present invention, a method for treating ajoint comprises positioning a first intramedullary stem in a firstmedullary canal of a first bone, positioning a second intramedullarystem in a second medullary canal of a second bone, coupling the firstintramedullary stem to the second intramedullary stem with a couplingmember therebetween, and delivering a therapeutic agent to the first andsecond medullary canals.

In some embodiments, the coupling member may comprise an adjustableheight manifold, and the method may further comprise actuating theadjustable height manifold, thereby adjusting a distance between a firstend of the first intramedullary stem and a first end of the secondintramedullary stem. Actuating the adjustable height manifold maycomprise rotating a nut coupled to a housing of the adjustable heightmanifold, and rotating the nut can move an adjustable connector of theadjustable height manifold relative to the housing.

In some embodiments, the coupling member may comprise a wedge elementhaving a fixed height, and the method may further comprise selecting awedge element from a plurality of wedge elements having different fixedheights. Coupling the first stem to the second stem with the couplingmember may comprise coupling the first intramedullary stem to the secondintramedullary stem with the selected wedge element therebetween,thereby adjusting a distance between a first end of the firstintramedullary stem and a first end of the second intramedullary stem.

In some embodiments, positioning the first intramedullary stem in thefirst medullary canal or positioning the second intramedullary stem inthe second medullary canal may comprise engaging a plurality ofprotrusions on the first or second stem with bone lining the respectivefirst or second medullary canal.

In some embodiments, delivering the therapeutic agent may comprisedelivering an antibiotic, wherein the antibiotic may comprisevancomycin, tobramycin, or a combination thereof.

In some embodiments, delivering the therapeutic agent may comprisedelivering the therapeutic agent from one or more outlet holes disposedin a fluted region of the first stem or the second stem.

In some embodiments, the first bone may be a femur and the second bonemay be a tibia.

In some embodiments, coupling may comprise engaging a flanged region inthe adjustable height manifold with a recessed region in the first endof the first stem or the second stem.

In some embodiments, delivering the therapeutic agent may comprisepumping the therapeutic agent from the first stem or the second stem tothe respective first or second medullary canal.

The method may further comprise suctioning unwanted fluids from thefirst or the second medullary canal, wherein the unwanted fluids passthrough one or more holes in the first stem or the second stem.

In some embodiments, positioning the first stem or the second stem maycomprise positioning the first stem or the second stem in the respectivemedullary canal such that 50% or less of a surface area of the firststem or the second stem contacts bone in the respective first or secondmedullar canal.

In another aspect of the present invention, a therapeutic agent deliverysystem comprises a femoral head configured to be disposed in anacetabulum, and a femoral stem coupled to the femoral head, the femoralstem configured to be disposed in a femoral medullary canal. The systemmay further comprise an inlet coupled to the femoral stem, and aplurality of outlets in the femoral head or the femoral stem. Thetherapeutic agent may be introduced into the system from the inlet, andthe therapeutic agent may be deliverable from the plurality of outletsinto the acetabulum or the femoral medullary canal.

In some embodiments, the femoral stem may comprise a threaded neckregion, the threaded neck region configured to be threadably engagedwith the femoral head thereby allowing adjustment of a distance betweenthe femoral head and the femoral stem.

In some embodiments, the femoral stem may comprise a plurality ofprotrusions extending axially along a longitudinal axis of the femoralstem.

In some embodiments, the femoral stem may comprise an elongate channelextending therethrough, the channel fluidly coupled with the inlet andthe plurality of outlets. The elongate channel may be a through hole,wherein one end of the femoral stem comprises a plug.

In some embodiments, the femoral stem may be tapered.

In some embodiments, the plurality of outlets may be disposed in thefemoral head. The femoral head may comprise a central channel, thecentral channel fluidly coupled with the plurality of outlets via aplurality of channels extending radially outward from the centralchannel.

The therapeutic agent delivery system may further comprise an outlet forfluid removal from the femoral head or the femoral stem.

The therapeutic agent delivery system may further comprise an acetabularcup coupled to the femoral head, wherein the therapeutic agent isdelivered from the acetabular cup to the acetabulum.

In some embodiments, the plurality of outlets may comprise a pluralityof holes having varying diameters.

In some embodiments, the femoral head may be at least partially hollow.

The therapeutic agent delivery system may further comprise a lockingmechanism for locking the femoral head with the femoral stem.

In another aspect of the present invention, a method for treating ajoint comprises positioning a femoral stem in a medullary canal of afemur, coupling a femoral head with the femoral stem, positioning thefemoral head in an acetabulum, and delivering a therapeutic agent to themedullary canal and the acetabulum.

In some embodiments, the coupling may comprise adjusting a distancebetween the femoral head and the femoral head. In some embodiments, thecoupling may comprise threadably engaging the femoral head with thefemoral stem.

In some embodiments, positioning the femoral stem may comprise engaginga plurality of protrusions on the femoral stem with bone lining themedullary canal.

In some embodiments, delivering the therapeutic agent may comprisedelivering an antibiotic, wherein the antibiotic may comprisevancomycin, tobramycin, or a combination thereof.

In some embodiments, delivering the therapeutic agent may comprisedelivering the therapeutic agent from one or more outlet holes disposedin a fluted region of the femoral stem.

In some embodiments, delivering the therapeutic agent may comprisepumping the therapeutic agent from the femoral stem to the medullarycanal or from the femoral head to the acetabulum.

The method may further comprise suctioning unwanted fluids from themedullary canal or the acetabulum.

In some embodiments, positioning the femoral stem may comprisepositioning the femoral stem into the medullary canal such that 50% orless of a surface area of the femoral stem contacts bone in themedullary canal.

In another aspect of the present invention, a device for delivering atherapeutic agent to a joint in a patient comprises an implant having aplurality of outlets for delivering the therapeutic agent to the joint,wherein the joint is a shoulder joint, an ankle joint, or a spinaljoint.

These and other embodiments are described in further detail in thefollowing description related to the appended drawing figures.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1A is a perspective view of an exemplary therapeutic agent deliverysystem for a knee;

FIG. 1B is an exploded view of the therapeutic agent delivery system ofFIG. 1A;

FIG. 2A is a perspective view of an exemplary intramedullary stem;

FIGS. 2B and 2C are side views of an exemplary intramedullary stem;

FIGS. 3A and 3B show alternative embodiments of the elongate body of anintramedullary stem;

FIG. 4A shows an exemplary embodiment of an adjustable height manifoldin a collapsed configuration;

FIG. 4B shows the adjustable height manifold of FIG. 4A in an extendedconfiguration;

FIG. 5 is an exploded view of the adjustable height manifold of FIG. 4A;

FIG. 6A is a perspective view of an exemplary embodiment of a housing ofthe adjustable height manifold of FIG. 4A;

FIG. 6B is a side view of the housing of FIG. 6A;

FIG. 6C is a top view of the housing of FIG. 6A;

FIG. 6D is a bottom view of the housing of FIG. 6A;

FIG. 6E is a vertical cross sectional view of the housing of FIG. 6A;

FIG. 7A is a perspective view of an exemplary embodiment of a rotatingnut of the adjustable height manifold of FIGS. 4A-4B;

FIG. 7B is a top view of the rotating nut of FIG. 7A;

FIG. 7C is a vertical cross sectional view of the rotating nut of FIG.7A;

FIG. 8A is a perspective view of an exemplary embodiment of anadjustable connector of the adjustable height manifold of FIGS. 4A-4B;

FIG. 8B is a bottom view of the adjustable connector of FIG. 8A;

FIGS. 8C and 8D are side views of the adjustable connector of FIG. 8A;

FIG. 9 shows an exemplary embodiment of a manifold pin of the adjustableheight manifold of FIGS. 4A-4B;

FIG. 10A is a top view of the assembled adjustable height manifold inthe collapsed configuration, as shown in FIG. 4A;

FIG. 10B is a vertical cross sectional view of the assembled adjustableheight manifold of FIG. 10A;

FIG. 11A is a perspective view of an exemplary embodiment of a fixedheight wedge;

FIGS. 11B and 11C are side views of the fixed height wedge of FIG. 11A;

FIGS. 12A-12H illustrate an exemplary mechanism for coupling anintramedullary stem to a coupling member;

FIGS. 13A-13C illustrate another exemplary mechanism for coupling anintramedullary stem to a coupling member;

FIGS. 14A-14D illustrate another exemplary mechanism for coupling anintramedullary stem to a coupling member;

FIG. 15 shows a method of treating a knee with a therapeutic agentdelivery system;

FIG. 16 shows a method of treating a knee with a therapeutic agentdelivery system;

FIG. 16 shows an exemplary embodiment of a therapeutic agent deliverysystem;

FIG. 17A is a perspective view of an exemplary therapeutic agentdelivery system for a hip;

FIG. 17B is an exploded view of the therapeutic agent delivery system ofFIG. 17A;

FIG. 18A is a perspective view of an exemplary embodiment of a femoralstem;

FIG. 18B is a side view of the femoral stem of FIG. 18A;

FIG. 18C is a side cross-sectional view of the femoral stem of FIG. 18A;

FIG. 18D is a bottom view of the femoral stem of FIG. 18A;

FIG. 19 shows an exemplary embodiment of a stem plug;

FIG. 20A is a side view of an exemplary embodiment of a femoral head;

FIG. 20B is a side cross-sectional view of the femoral head of FIG. 20A;

FIGS. 21A and 21B are side cross-sectional views of another exemplaryembodiment of a femoral head;

FIG. 22 is a side cross-sectional view of another exemplary embodimentof a femoral head;

FIGS. 23A and 23B show exemplary mechanisms for coupling a femoral headto a femoral stem;

FIGS. 24A and 24B show an exemplary mechanism for locking a set distancebetween a femoral head and a femoral stem;

FIGS. 24C-24F illustrate a method of assembling the locking mechanism ofFIGS. 24A and 24B;

FIGS. 25A and 25B show an exemplary embodiment of a therapeutic agentdelivery system having an acetabular cup;

FIG. 26 shows an exemplary embodiment of a therapeutic agent deliverysystem for a hip;

FIG. 27 shows a method of treating a hip using a therapeutic agentdelivery system;

FIGS. 28A and 28B illustrate the use of negative pressure wound therapywith an intramedullary device;

FIG. 29 shows an optional cover for an intramedullary stem;

FIG. 30 shows an exemplary embodiment of a therapeutic agent deliverysystem;

FIGS. 31A and 31B show exemplary embodiments of therapeutic agentdelivery systems with inlets and outlets;

FIGS. 32A and 32B illustrate an exemplary configuration for the internalchannels of an intramedullary device;

FIGS. 33A-33C illustrate another exemplary configuration for theinternal channels of an intramedullary device; and

FIGS. 34-36 show exemplary embodiments of therapeutic agent deliverysystems.

DETAILED DESCRIPTION OF THE INVENTION

Specific embodiments of the disclosed device, delivery system, andmethod will now be described with reference to the drawings. Nothing inthis detailed description is intended to imply that any particularcomponent, feature, or step is essential to the invention.

Described herein are therapeutic agent delivery systems that may be usedin a knee joint, a hip joint, or any other joint. For example, thetherapeutic agent delivery system may be used to treat a shoulder orankle joint, or a portion of the spine. One of skill in the art willappreciate that other joints may also be treated with the systems,devices, and methods disclosed herein. Optionally in any embodiment, thetherapeutic agent delivery system may comprise one or moreintramedullary stems, configured to be disposed stably in a medullarycanal of a bone. The intramedullary stem may be configured to deliverthe therapeutic agent to the medullary canal, the joint space, or acombination thereof. Optionally, in any embodiment, an intramedullarystem is coupled to another component, such as another intramedullarystem or a femoral head, in a way that allows the distance between thestem and the other component to be adjusted to fit a patient, or thedistance therebetween may be fixed.

The therapeutic agent delivered by the delivery systems described hereinmay comprise any fluid. For example, the therapeutic agent may comprisean antibiotic fluid such as a vancomycin or tobramycin, combinationsthereof, or other antibiotics commonly used to treat implant-associatedinfections. One of skill in the art will appreciate that any therapeuticagent may be also be delivered alone, or in combination with anantibiotic or other therapeutic agent. Other exemplary therapeuticagents may include saline or other fluids used to irrigate the joint ormedullary canals being treated.

Therapeutic Agent Delivery System for Knee

FIGS. 1A and 1B show an exemplary therapeutic agent delivery system 100for a knee. FIG. 1A shows the components of the delivery systemassembled together, while FIG. 1B shows the components of the deliverysystem disassembled and aligned for assembly. The delivery system 100comprises a first intramedullary stem 110, a second intramedullary stem120, and a coupling member 130. Each of the two intramedullary stems 110and 120 can be configured be disposed in a medullary canal of a bone.For example, the first intramedullary stem 110 can be configured to bedisposed in the medullary canal of a femur of a patient, while a secondintramedullary stem 120 can be configured to be disposed in themedullary canal of a tibia of the patient. The coupling member 130,configured to be disposed in the joint space, can couple the two stemsin a stable configuration, while maintaining a desired distance 105between the two stems throughout the length of use of the therapeuticagent delivery system in a patient.

The first intramedullary stem 110 and the second intramedullary stem 120may be any intramedullary stem as described herein. The two stems may betwo identical stems, or they may be two different stems, configured tohave one or more differences in dimensions, configurations, or features.For example, the delivery system may comprise a first intramedullarystem specifically configured to engage a femur, and a secondintramedullary stem specifically configured to engage a tibia. The twostems may differ in one or more dimensions, such as length, diameter, ordegree of taper. Alternatively or in combination, the two stems maydiffer in one or more configurations or features as described herein(e.g., configuration of the stem channel, number, shape, and size of theprotrusions, the fluted regions, and/or the outlet holes, etc.).

The coupling member 130 may comprise any coupling member as describedherein, such as an adjustable height manifold or a fixed height wedge.In many embodiments of the delivery system 100, the coupling member 130can be configured to allow the distance 105 between the two stems to beadjusted, so as to accommodate the anatomy of the patient. The couplingmember can be configured to fluidly couple to a source of a therapeuticagent and receive the therapeutic agent, and distribute the therapeuticagent to the intramedullary stems for delivery to the medullary canals.

The first stem 110 and the second stem 120 may be releasably coupled tothe coupling member 130. Each of the first stem and the second stem maybe configured to couple to a stem connector 132 of the coupling member.The first stem may couple to a first stem connector 132 a, and thesecond stem may couple to a second stem connector 132 b. Variousmechanisms for the connection between the stem and the coupling memberare described herein, any of which may be incorporated into the couplingmember 130 for coupling with the first stem or the second stem. Thefirst stem and the second stem may couple to the first stem connectorand the second stem connector, respectively, via identical mechanisms orvia different mechanisms. Accordingly, the first stem connector 132 aand the second stem connector 132 b of the coupling member may beidentical or different. In preferred embodiments, the first stem and thesecond stem are identical, such that the coupling member accordinglycomprises two identical stem connectors configured to couple to thefirst stem and the second stem via identical mechanisms.

Intramedullary Stem

FIGS. 2A-2C show an exemplary intramedullary stem 200, suitable forincorporation with a therapeutic agent delivery system for a knee. FIG.2A is a perspective view, and FIGS. 2B and 2C are side views of theintramedullary stem 200. Each intramedullary stem 200 comprises anelongate body 205 having a longitudinal axis 210, the elongate bodyhaving a first end 215 and a second end 220 opposite the first end. Thefirst, or proximal, end may be configured to couple to a coupling member130, such as an adjustable height manifold or a fixed height wedge asdescribed herein. The second, or distal, end may be disposed in themedullary canal of a bone. The elongate body 205 comprises a stemchannel 225 extending between the first end 215 and the second end 220,the stem channel configured to deliver the therapeutic agent through thestem and to the medullary canal. The first end 215 of the intramedullarystem 200 may be configured to couple the stem to a coupling member. Thefirst end may comprise any mechanism for connecting the stem to thecoupling member (e.g., flanged region, dovetail joints, snap buckle,winged nut, etc.), as described in further detail herein.

The intramedullary stem 200 may comprise a plurality of protrusions 230,protruding radially outward from the elongate body 205. The plurality ofprotrusions may comprise any number of protrusions having anyappropriate shape, size, or configuration to engage the medullary canalin a stable fashion. For example, the protrusions may comprise elongatefins extending along the longitudinal length of the elongate body, asshown in FIGS. 2A-2C. In one exemplary embodiment, the plurality ofprotrusions may comprise four fins, spaced equally at about 90° aboutthe longitudinal axis 210 of the elongate body. The plurality ofprotrusions 230 and the elongate body 205 may be formed separately andcoupled together. Alternatively or in combination, the plurality ofprotrusions 230 may be formed by removing material from the elongatebody 205, such that the plurality of protrusions and the elongate bodyare formed as a single member. Adjacent protrusions 230 may define oneor more fluted regions 235 therebetween, the fluted regions radiallyrecessed compared to the protrusions. The fluted regions may form aconcave recessed region between adjacent protrusions.

The plurality of protrusions and fluted regions can be configured tominimize the surface area of the stem contacting the bone lining themedullary canal, such that the area of the bone flushed with thetherapeutic agent may be maximized. For example, the plurality ofprotrusions and fluted regions can be configured such that less than 50%of the surface area of the stem is in contact with the bone lining themedullary canal. Of course this is not intended to be limiting and oneof skill in the art will appreciate that any percentage of the surfacearea of the stem may contact the bone. The stem may comprise a pluralityof identical fluted regions defined by a plurality of elongate fins,distributed symmetrically about the longitudinal axis 210 of the stem,as shown in FIGS. 2A-2C. Alternatively, a plurality of fluted regionsmay be distributed asymmetrically about the longitudinal axis of thestem, and/or may have different shapes or sizes as described in furtherdetail herein.

An intramedullary stem 200 may further comprise a plurality of outletholes 240 in fluid communication with the stem channel 225. Theplurality of outlet holes 240 may be configured to deliver thetherapeutic agent, distributed through the stem channel 225, to themedullary canal, as well as adjacent tissue including the joint. Theplurality of outlet holes may be disposed in a fluted region 235, so asto deliver the therapeutic agent to the area of the bone not in contactwith the intramedullary stem. The plurality of outlet holes may compriseany number of outlet holes having any appropriate size, shape, ordistribution. For example, the plurality of outlet holes may include aplurality of equally sized and spaced holes that extend axially along aline substantially parallel to the longitudinal axis 210 of the stem, asshown in FIGS. 2A-2C. The plurality of outlet holes may be arranged invarious configurations, as described in further detail herein. Theplurality of outlet holes may comprise holes having an identical shapeand/or size, or holes having various shapes and/or sizes. Varying thehole size may allow further fluid control of therapeutic agent as itexits different regions of the stem.

The stem channel 225 may be a through hole that extends from the firstend 215 to the second end 220 through both the first end and the secondend, such that the elongate body comprises an open second or distal end.The system may further comprise a plug (not shown) configured to coupleto the open second end of the stem, so as to close the second end andthereby create a blind channel. Alternatively, the stem channel 225 maybe a blind channel, wherein the second end of the elongate body isclosed. In configurations wherein the second end is open, thetherapeutic agent may exit the stem channel into the medullary canalthrough the second end and/or through a plurality of outlet holesdisposed along the elongate body 205 as described herein. If the stemcomprises only the stem channel 225 extending through the first andsecond ends, without the plurality of outlet holes, the therapeuticagent may exit the stem channel only through the second end. Inconfigurations wherein the second end of the stem is closed, thetherapeutic agent may exit the stem channel into the medullary canalonly through the plurality of outlet holes.

The intramedullary stem 200 may be tapered to fit the medullary canal.For example, the elongate body 205 and/or the plurality of protrusions230 may be tapered from the first end 215 to the second end 220, asshown, so as to have a smaller radial cross-sectional area at the secondend than at the first end. For example, the taper may comprise a gradualtaper, wherein the extent of the taper may be preferably in a range fromabout 0.1° to about 10°, more preferably about 0.5° to about 5°, andeven more preferably about 1° to about 5°, or about 1° to about 4°, orabout 2° or about 3°. The taper may be adjusted to accommodate amedullary canal of a specific type of bone.

The exemplary embodiment of FIGS. 2A-2C may comprise one or both of twointramedullary stems of a therapeutic agent delivery system for a kneeas shown in FIGS. 1A and 1B. Preferably, the therapeutic agent deliverysystem for a knee comprises two identical intramedullary stems, such asthe exemplary embodiment of FIGS. 2A-2C.

FIGS. 3A and 3B show alternative embodiments of the elongate body 205 ofthe intramedullary stem 200 of FIGS. 2A-2C. FIG. 3A shows an elongatebody 205 comprising one or more protrusions 231 spirally disposed aroundthe elongate body 205 along the longitudinal length of the body.Adjacent spiral or helical protrusions 231 define one or more flutedregions 236 therebetween, also spirally disposed around the elongatebody. FIG. 3B shows an elongate body 205 comprising a plurality ofprotrusions 232 resulting from cutting away or otherwise removingportions of the spirally disposed protrusions 231 shown in FIG. 3A. Forexample, as shown, a plurality of radial cuts may be made to elongatebody to define the plurality of protrusions 232. A plurality of flutedregions 237 may be defined between remaining portions of adjacenthelical protrusions. Cutting away or removing portions of the spiralprotrusions 231 as shown in FIG. 3B can further decrease the contactarea between the stem and the bone, thus allowing the therapeutic agentto flow more freely along the medullary canal.

In the embodiment of FIG. 3A, a plurality of outlet holes (not shown)may extend along a helical or spiral line, such as along the helical orspiral fluted regions 236. In the embodiment shown in FIG. 3B, theplurality of outlet holes 240 may disposed in the fluted regions 237,such that the holes extend about a plurality of rings around thecircumference of the elongate body.

Adjustable Height Manifold

FIGS. 4A and 4B show an adjustable height manifold 300 suitable forincorporation with a therapeutic agent delivery system for a knee suchas in FIGS. 1A-1B. The adjustable height manifold 300 is one example ofa coupling member that can couple the two intramedullary stems in astable configuration, while maintaining a desired distance between thetwo stems throughout the length of use of the therapeutic agent deliverysystem in a patient. The adjustable height manifold further enables theadjustment of the distance between the two stems, such that the deliverysystem may be configured to optimally accommodate the anatomy of thepatient. The adjustable height manifold 300 may comprise a housing 315,a rotating nut 320, and an adjustable connector 325. The rotating nut320 and adjustable connector 325 may be coupled to the housing 315, andconfigured so as to allow the manifold height 305 to be increased ordecreased, based on the desired set distance between the two stems for apatient. Rotating the nut 320 in clockwise and counterclockwisedirections can collapse or extend the manifold, by translating theadjustable connector along a longitudinal axis 310 of the manifold. FIG.4A shows the adjustable height manifold 300 in a collapsedconfiguration, such that the manifold height 305 is relatively short andthe manifold can thus fit a patient who requires a shorter set distancebetween the two knee stems. FIG. 4B shows the adjustable height manifold300 in an extended configuration, such that the manifold height 305 isrelatively long and the manifold can thus fit a patient who requires alonger set distance between the two knee stems.

The adjustable height manifold 300 further comprises a first stemconnector 342 and a second stem connector 344, disposed on oppositesides of the housing. The first stem connector 342 may be configured tocouple to a first end of a first intramedullary stem, and the secondstem connector 344 may be configured to couple to a first end of asecond intramedullary stem. The first stem connector 342 may be coupledto the adjustable connector 325, while the second stem connector 344 maybe coupled to the housing 315. Each stem connector may comprise aconnection mechanism to couple to a corresponding connection mechanismdisposed on the first end of the intramedullary stem. The first andsecond stem connectors may comprise different connection mechanisms, orthey may comprise identical connection mechanisms. In preferredembodiments, the first and second stem connectors comprise identicalconnection mechanisms, and have a fixed orientation relative to oneanother, such that the orientation remains the same during actuation ofthe adjustable height manifold to adjust the manifold height. The fixedorientation of the two stem connectors relative to one another can allowproper and simultaneous coupling of the manifold to each stem during theimplantation of the delivery system in a patient using the sameactuation motion for both stems.

FIG. 5 is an exploded view of the adjustable height manifold 300 ofFIGS. 4A-4B. The adjustable height manifold 300 comprises a housing 315,a rotating nut 320 having a scalloped outer surface to provide grippingregions for an operator's fingers and internal threads, and anadjustable connector 325, wherein the three components are axiallyaligned along a longitudinal axis 310 of the manifold. The manifoldfurther comprises a manifold pin 330, configured to secure the couplingof the adjustable connector the housing and control the range of motionof the adjustable connector. The adjustable connector comprises a firststem connector 342, configured to couple to a first intramedullary stem.The housing comprises a second stem connector 344, configured to coupleto a second intramedullary stem. The housing further comprises an inlet335 coupled thereto, the inlet configured to fluidly couple to a sourceof the therapeutic agent (not shown) to be delivered to the patient. Thehousing is configured to couple to the rotating nut and slidably receivethe adjustable connector. The rotating nut is configured to threadablyengage the adjustable connector, so as to cause the adjustable connectorto extend outwards from housing along the longitudinal axis 310, orretract inwards into the housing along the longitudinal axis when thenut is rotated.

FIGS. 6A-6E show an exemplary embodiment of a housing 315 of theadjustable height manifold 300 of FIGS. 4A-4B. FIG. 6A is a perspectiveview, FIG. 6B is a side view, FIG. 6C is a top view, FIG. 6D is a bottomview, and FIG. 6E is a vertical cross sectional view (cross section A-Aof FIG. 6B) of the housing 315. The housing 315 comprises an inlet 335to fluidly couple to a source of the therapeutic agent, and a housingchannel 340 (best seen in FIG. 6E) extending along the longitudinal axis310 through the housing. The housing channel 340 is in fluidcommunication with the inlet 335, such that the therapeutic agent addedto the therapeutic agent delivery system through the inlet can bedistributed to other components of the delivery system through thehousing channel. The inlet 335 may comprise a barbed outer surface, tosecurely engage the inner surface of a tube (best seen in FIG. 28A)supplying the therapeutic agent. The housing may further comprise aconcave groove 345, disposed at least partially or completely about thecircumference of the housing thereby minimizing profile of thetubing/housing assembly. The groove can allow for placement of tubingsupplying the therapeutic agent, coupled to the inlet 335.

The housing 315 further comprises a second stem connector 344,configured to couple to an intramedullary stem such as anyintramedullary stem described herein. The housing channel 340 can extendthrough the stem connector 344, such that the housing channel can befluidly coupled to a stem channel of a stem coupled to the stemconnector. The stem connector 344 may comprise any mechanism forconnecting the coupling member to the stem (e.g., flanged region,dovetail joints, snap buckle, winged nut, etc.), as described in furtherdetail herein.

The housing channel 340 may be configured to have a geometry that allowsthe adjustable connector disposed in the channel to slide axially alongthe longitudinal axis 310, while preventing the adjustable connectorfrom rotating within the channel. For example, the channel 340 maycomprise two flat inner surfaces 347 disposed opposite one another,configured to interface with two flat side surfaces of the of adjustableconnector. The channel may further comprise two rounded side innersurfaces 349, configured to interface with two corresponding roundedsurfaces of the adjustable connector. For example, the rounded innersurfaces 347 may comprise concave surfaces, while the rounded sidesurfaces of the adjustable connector may comprise convex surfaces. Theinterfacing of the flat inner surfaces of the housing channel with theflat side surfaces of the adjustable connector can prevent theadjustable connector from rotating therein, ensuring that the adjustableconnector moves only slidably, not rotatably, within the housingchannel. Preventing rotation of the adjustable connector, whichcomprises the first stem connector 342, can ensure that the orientationof the second stem connector 344 remains fixed with respect to theorientation of the first stem connector, even when the rotating nut 320is rotated. The fixed orientation of the first and second stemconnectors with respect to one another can ensure that the manifold caneasily couple to both the first stem and the second stem. For example,the manifold can be inserted into the space between the first and secondstems and then rotated in one direction to couple to both stems. Such aconfiguration of the stem connectors can facilitate the implantation ofthe delivery system in a patient, by obviating the potential need torotate one or more intramedullary stems after the stems have alreadybeen inserted into the patient's medullary cavities.

The housing may further comprise one or more prongs 355, disposed aboutthe periphery of the housing channel 340 and projecting longitudinallyfrom housing. The prongs may comprise four prongs as shown in FIGS.6A-6E, each internal surface of the prong configured to engage each ofthe four sides of the adjustable connector to be disposed in the housingchannel. Two of the prongs, disposed opposite one another, can beconfigured to have the flat inner surfaces 347 of the housing channel,while two of the remaining prongs, also disposed opposite one another,can be configured to have the rounded inner surfaces 349 of the housingchannel. One or more of the prongs may further comprise an outwardfacing lip 357 disposed at the edge of the prong. The lip 357 may beconfigured to engage a corresponding manifold groove in the rotating nutas described in further detail herein, so as to securely couple therotating nut to the housing and prevent axial movement of the rotatingnut along the longitudinal axis 310 during rotation of the nut. The lip357 may further comprise chamfers 359, configured to facilitate thecoupling of the rotating nut to the housing by guiding the lip into themanifold groove of the nut.

The housing may further comprise a housing pin hole 360, configured toreceive a portion of the manifold pin. The pin hole 360 may be disposedon a prong 355 configured to engage the rotating nut, such that the pinhole 360 can be aligned with a nut pin hole in the rotating nut alsoconfigured to receive the manifold pin. When fully assembled, themanifold pin can be disposed partially in the housing and partially inslot in the adjustable connector disposed within the housing channel, tocreate a hard stop to prevent the manifold assembly from coming apart,as described in further detail herein. The housing pin hole 360 may bedimensioned to ensure the retention of the manifold pin within the pinhole. For example, the housing pin hole can have a diameter that issubstantially equal to the diameter of the portion of the manifold pinconfigured to be disposed in the housing, such that the pin can be pressfit into the housing pin hole.

FIGS. 7A-7C show an exemplary embodiment of a rotating nut 320 of theadjustable height manifold 300 of FIGS. 4A-4B. FIG. 7A is a perspectiveview, FIG. 7B is a top view, and FIG. 7C is a vertical cross sectionalview (cross section A-A of FIG. 7B) of the rotating nut 320. Therotating nut 320 comprises a plurality of threads 362 disposed on aportion of its inner surface. The threads 362 may be configured toengage corresponding threads on a portion of the adjustable connector,such that rotation of the nut 320 about the adjustable connector cancause axial movement of the adjustable connector along the longitudinalaxis of the manifold. The nut 320 may further comprise a manifold groove364 disposed circumferentially about the inner surface of the nut. Themanifold groove may be configured to receive one or more lips disposedon one or more prongs of the housing as described herein, so as to lockthe nut onto the housing while still allowing rotation of the nutrelative to the housing. The nut may further comprise chamfers 366disposed below the manifold groove, extending circumferentially aboutthe inner surface of the nut. The chamfers 366 can be configured tocorrespond to the chamfers of a housing lip, so as to guide the lip intothe manifold groove. The nut may further comprise a nut pin hole 368disposed on a portion of the nut below the threads 362, the nut pin holeconfigured to receive the manifold pin therethrough. During assembly ofthe manifold, the manifold pin may be pushed into and completely throughthe body of the rotating nut, to dispose the pin partially within thehousing and partially within the adjustable connector and therebyavoiding physical obstruction of the rotation of the nut by the pin.Accordingly, when the manifold is completely assembled, the manifold pindoes not traverse any portion of the rotating nut, such that therotating nut can rotate freely. The nut pin hole 368 may be dimensionedto facilitate the insertion of the manifold pin into and through the pinhole. For example, the nut pin hole can have a diameter that is greaterthan the diameter of the largest portion of the manifold pin, such thatthe pin can easily pass through the nut pin hole.

FIGS. 8A-8D show an exemplary embodiment of an adjustable connector 325of the adjustable height manifold 300 of FIGS. 4A-4B. FIG. 8A is aperspective view, FIG. 8B is a bottom view, and FIGS. 8C and 8D are sideviews. The adjustable connector 325 comprises an adjustable connectorchannel 370 extending axially along the longitudinal axis 310. Thechannel 370 extends through the length of the adjustable connector, andis configured to be in fluid communication with the housing channel 340and hence with the inlet 335 fluidly coupled to the housing channel. Theadjustable connector further comprises a first stem connector 342,configured to couple to an intramedullary stem such as anyintramedullary stem described herein. The connector channel 370 extendsaxially through the stem connector 342, such that the channel 370 is influid communication with the stem channel of the stem coupled to thefirst stem connector 342. The stem connector 342 may comprise anymechanism for connecting the coupling member to the stem (e.g., flangedregion, dovetail joints, snap buckle, winged nut, etc.), as described infurther detail herein.

The adjustable connector may further comprise threads 372 configured toengage corresponding threads of the rotating nut, such that rotation ofthe nut can cause vertical movement of the adjustable connector into orout of the housing. The adjustable connector may comprise two flat sidesurfaces 327 and the two rounded side surfaces 329, wherein the flatside surfaces may be configured to interface with the flat innersurfaces of the housing channel, and wherein the rounded side surfacesmay be configured to interface with the rounded inner surfaces of thehousing channel. As described herein, such a configuration can preventthe adjustable connector from rotating when the rotating nut is rotated,ensuring that the orientation of the adjustable connector and hence thefirst stem connector 342 remains constant with respect to theorientation of the second stem connector. Moreover, this translates therotational actuation of the nut into linear motion of the adjustableconnector.

FIG. 8C shows the proximal flat side surface 327 a of the adjustableconnector, configured to be oriented proximally with respect to theinlet of the housing. The proximal flat side surface can be configuredto have an open slot 374 that extends through the bottom of theadjustable connector. The open slot 374 may be fluidly coupled to theadjustable connector channel 370, as best seen in FIG. 8B showing thebottom view of the adjustable connector. The open slot 374 may beconfigured such that when the assembled manifold is in the collapsedconfiguration as shown in FIG. 4A, the open slot is aligned with theinlet so as to fluidly couple the inlet to the adjustable connectorchannel 370. When the assembled manifold is in the extended position asshown in FIG. 4B, the open bottom of the open slot 374 can ensure thatthe inlet remains in fluid communication with the housing channel, andthereby with the adjustable connector channel.

FIG. 8D shows the distal flat side surface 327 b of the adjustableconnector, configured to be oriented distally with respect to the inletof the housing. The distal flat side surface comprises a closed slot376, configured to engage a portion of the manifold pin retained in thehousing. As described herein, the manifold pin may be coupled to themanifold assembly after the housing, rotating nut, and adjustableconnector are assembled together. After full assembly, the manifold pinmay be partially disposed in the housing, and partially disposed in theclosed slot 376 of the adjustable connector. The manifold pin can beconfigured to remain engaged in the closed slot 376 during retraction orextension of the adjustable connector. The closed slot may be configuredto have a width that is greater than the diameter of the portion of themanifold pin disposed in the slot, so as to facilitate the movement ofthe adjustable connector. When the assembled manifold is in thecollapsed configuration as shown in FIG. 4A, the manifold pin may bealigned with the top of the closed slot 376. When the assembled manifoldis in the extended configuration as shown in FIG. 4B, the manifold pinmay be aligned with the bottom of the closed slot 376. The bottom of theclosed slot 376 provides a hard stop to the extension of the adjustableconnector from the housing, preventing the adjustable connector fromextending any further. Thus, the closed slot 376 and the manifold pincan prevent the manifold assembly from coming apart.

FIG. 9 shows an exemplary embodiment of a manifold pin 330 of theadjustable height manifold 300 of FIGS. 4A-4B. The manifold pin 330 maycomprise a small diameter portion 332 and a large diameter portion 334.The small diameter portion 332 may be configured to engage the closedslot in the adjustable connector, while the large diameter portion 334may be configured to be disposed in the manifold pin hole in thehousing. As described herein, the manifold pin may be coupled to themanifold assembly by inserting the pin through the nut pin hole in therotating nut. To facilitate the insertion of the manifold pin throughthe rotating nut, the large diameter portion 334 may have a diametersmaller than the diameter of the nut pin hole. To ensure the retentionof the manifold pin within the housing, the large diameter portion 334may have a diameter that is substantially equal to the diameter of thehousing pin hole, such that the large diameter portion press fits intothe housing pin hole. To facilitate translational motion of theadjustable connector within the housing channel, the small diameterportion 322 may have a diameter that is smaller than the width of theclosed slot of the adjustable connector.

FIG. 10A is a top view and FIG. 10B is a vertical cross sectional view(cross section A-A of FIG. 10A) of the assembled adjustable heightmanifold 300 in the collapsed configuration, as shown in FIG. 4A. Thehousing 315 is coupled to the rotating nut 320 via engagement of a lip357 with a manifold groove 364 of the nut. The adjustable connector 325is slidably disposed in the housing channel 340, and threadably engagedwith the rotating nut 320. The large diameter portion 334 of themanifold pin 330 is disposed in the housing pin hole 360, while thesmall diameter portion 332 is disposed within the closed slot 376 of theadjustable connector. When the rotating nut is rotated clockwise orcounterclockwise, the adjustable connector can slide up or down withinthe housing channel without rotating. The manifold pin can control theextent to which the adjustable connector may be extended, by providing ahard stop when the pin hits the bottom of the closed slot 376. The inlet335 of the housing can be coupled to a source of a therapeutic agent tobe delivered to the patient. The inlet can be fluidly connected to thehousing channel 340 either directly or indirectly through the open slot374 of the adjustable connector. When the manifold is in a collapsedconfiguration, the inlet can be fluidly coupled to the housing channelindirectly, through the open slot 374 of the adjustable connector. Whenthe manifold is in an extended configuration, the inlet may be fluidlycoupled directly to the housing channel. The housing channel can befluidly connected to the adjustable connector channel 370, so as tofluidly connect to the stem channel of the first stem, coupled to thefirst stem connector of the adjustable connector. The housing channelcan also be fluidly connected to the stem channel of the second stem,coupled to the second stem connector of the housing. Thus, thetherapeutic agent provided via the inlet 335 can be distributed to thefirst and second intramedullary stems coupled to the manifold.

Fixed Height Wedge

FIGS. 11A-11C show a fixed height wedge 400 suitable for incorporationwith a therapeutic agent delivery system for a knee. FIG. 11A shows aperspective view, and FIGS. 11B and 11C show side views of the wedge400. The fixed height wedge 400 is one example of a coupling member 130that can couple the two intramedullary stems in a stable configuration,while maintaining a desired distance between the two stems throughoutthe length of use of the therapeutic agent delivery system in a patient.The wedge provides a relatively simpler connection between twointramedullary stems, wherein the wedge comprises a single, monolithiccomponent rather than an assembly of a plurality of components. Whilethe wedge height 405 of a wedge is fixed, the wedge may be provided inmultiple sizes having various wedge heights, and the most appropriatesize may be selected for each patient according to the patient'sanatomy.

The fixed height wedge 400 comprises a first stem connector 442configured to couple to a first intramedullary stem, and a second stemconnector 444 configured to couple to a second intramedullary stem. Thefirst and second stem connectors may comprise any mechanism forconnecting the stem to the coupling member (e.g., flanged region,dovetail joints, snap buckle, winged nut, etc.), as described in furtherdetail herein. The wedge further comprises an inlet 435, configured tobe coupled to a source of a therapeutic agent to be delivered to thepatient. The inlet 435 can be fluidly connected to a wedge channel 440extending along the longitudinal axis 410 of the wedge, through both thefirst stem connector and the second stem connector. Thus, thetherapeutic agent provided through the inlet can be distributed via thewedge channel to the intramedullary stems coupled to the wedge.

The fixed height wedge 400 may additionally comprise one or more of anyapplicable structures and features described in relation to theadjustable height manifold 300. For example, the wedge may comprise aconcave groove 445, analogous to the concave groove 345 described inrelation to the housing of the adjustable height manifold. Similarly tothe concave groove 345, concave groove 445 may be disposed partiallyabout the circumference of the wedge, so as to provide for placement oftubing coupled to the inlet.

Coupling Mechanisms

FIGS. 12A-12H illustrate an exemplary mechanism for coupling anintramedullary stem 200 to a coupling member 130. The stem 200 maycomprise any embodiment of an intramedullary stem as described herein,and the coupling member 130 may comprise any embodiment of a couplingmember as described herein. The stem 200 comprises a first end 215configured to engage the coupling member, and the coupling member 130comprises a stem connector 132 configured to engage the first end of thestem. The stem connector 132 may be any stem connector coupled to anycoupling member as described (e.g., stem connector 342, 344, 442, 444,etc.). FIG. 12A is a perspective view of the first end 215 of theintramedullary stem 200. FIG. 12B is a perspective view of the stemconnector 132 of the coupling member 130. FIGS. 12C and 12D are sideviews of a therapeutic agent delivery system 100 before assembly. FIG.12E is a side view of an assembled delivery system 100 comprising twostems 200 and a coupling member 130 coupled together. FIG. 12F is anenlarged vertical cross sectional view of the portion of the assembledsystem 100 as indicated in FIG. 12C. FIGS. 12G and 12H are radial crosssections of the assembled system 100 along line A-A as indicated in FIG.12E, at different steps of the assembly.

As shown in FIG. 12A, the first end 215 comprises a raised portion 250disposed about a portion of the periphery of the first end. The raisedportion 250 defines a rounded cavity 251 therein, configured to receivea flanged region 150 of the coupling member 130 as shown in FIG. 12B.The raised portion 250 has a circumferential opening 252 configured toreceive the flanged region 150 of the coupling member therethrough. Theraised portion 250 further comprises a recessed lip 253 defining arecessed region 254, as best seen in FIG. 12F. The recessed region 254can receive and retain the flanged region 150, so as to limit axialmovement of the coupling member along the longitudinal axis 210 of thestem. As shown in FIGS. 12E and 12F, the flanged region 150 can have alength 154 that is longer than the width 152. The flanged region canfurther comprise two flat edges 157 extending along the length 154 ofthe flanged region, and two rounded edges 159 extending about the width152 of the flanged region. The circumferential opening 252 may have awidth that is greater than or equal to the width 152 of the flangedregion 150, but less than the length 154 of the flanged region, suchthat the flanged region can only enter the circumferential opening inthe vertical orientation 151 with respect to the circumferential opening252, as shown in FIG. 12G.

FIGS. 12C and 12D show the delivery system 100 before assembly, whereinthe coupling member 130 is aligned for insertion into the space betweentwo intramedullary stems 200. The flanged regions 150 of the first stemconnector 132 a and second stem connector 132 b are in the verticalorientation with respect to the circumferential openings 252 of theraised portions of the intramedullary stems. While aligned in thisorientation, the coupling member may be pushed into the space betweenthe two intramedullary stems such that the flanged regions are insertedthrough the circumferential openings of each stem, and captured into therecessed regions of the raised portions as shown in FIGS. 12E, 12F, and12G.

Once the flanged region 150 is placed within the rounded cavity 251, theflanged region may be rotated in the direction shown by arrow 155, asshown in FIG. 12G. The flanged region may be rotated until the flangedregion is disposed in the horizontal orientation 153 with respect to thecircumferential opening 252, as shown in FIG. 12H. In the horizontalorientation, the flanged region can be prevented from sliding out of therounded cavity through the circumferential opening, since the length 154of the flanged region is greater than the size of the opening 252. Thefirst end 215 may further comprise one or more pins 255 disposedtherein, configured to further secure the coupling between the stem andthe stem connection. For example, the first end 215 may comprise twopins 255, each pin angularly spaced at about 90° from the center of thecircumferential opening 252. Each rounded edge 159 of the flanged region150 may comprise a smaller diameter edge 159 a and a larger diameteredge 159 b, such that a notch 156 is created at the intersection ofedges 159 a and 159 b. As described, the flanged region 150 may beinserted through the opening 252 in the vertical orientation 151 asshown in FIG. 12G, and subsequently rotated in the direction shown byarrow 155, within the recessed region 254 of the first end 215. As theflanged region rotates, the pin 255 can slide against the smallerdiameter edge 159 a, until the pin hits the notch 156 created by thelarger diameter edge 159 b. The pins may be configured, for example, toallow the flanged region to rotate by about 90° or a quarter turn beforehitting the pins. The engagement of the notch 156 with the pin 255 canprevent further rotation of the stem relative to the coupling member.The pins 255 can thus provide a hard stop to the rotation of the flangedregion, ensuring that the final orientation of the flanged region is thehorizontal orientation 153, which can prevent the flanged region fromsliding out of the rounded cavity as described herein.

FIGS. 13A-13C illustrate another exemplary mechanism for coupling anintramedullary stem to a coupling member 130. FIG. 13A shows aperspective view and FIG. 13B shows a top view of the coupling member130 comprising the exemplary connection mechanism. FIG. 13C shows a sideview of a portion of an assembled delivery system 100, comprising twostems 200 and a coupling member 130 coupled together. The stem 200 maycomprise any embodiment of an intramedullary stem as described herein,and the coupling member 130 may comprise any embodiment of a couplingmember as described herein. The stem 200 comprises a first end 215configured to engage the coupling member, and the coupling member 130comprises a stem connector 132 configured to engage the first end of thestem. The stem connector 132 may be any stem connector coupled to anycoupling member as described (e.g., stem connector 342, 344, 442, 444,etc.). Each stem connector 132 may comprise one or more dovetailedregions 160, configured to engage one or more corresponding dovetailedregions 260 of the first end 215 of the stem 200. Each stem connector132 may further comprise a snap buckle 162, configured to engage acorresponding snap buckle (not shown) disposed on the first end 215 ofthe stem. The snap buckle 162 can comprise flexible stems 164 that cantension centrally when the coupling member 130 is inserted slidinglyinto the stems 200. The coupling member can snap into place when thecoupling member is pushed past the notch 166 within the stems.

FIGS. 14A and 14B illustrate another exemplary mechanism for coupling anintramedullary stem 200 to a coupling member 130. FIG. 14A shows thefirst step of assembly of the stems and the coupling member using theexemplary mechanism, and FIG. 14B shows the second step of the assembly.The stem 200 may comprise any embodiment of an intramedullary stem asdescribed herein, and the coupling member 130 may comprise anyembodiment of a coupling member as described herein. The stem 200comprises a first end 215 configured to engage the coupling member, andthe coupling member 130 comprises a stem connector 132 configured toengage the first end of the stem. The stem connector 132 may be any stemconnector coupled to any coupling member as described (e.g., stemconnector 342, 344, 442, 444, etc.). Each stem connector 132 maycomprise one or more dovetailed regions 160, configured to engage one ormore corresponding dovetailed regions 260 of the first end 215 of thestem 200. FIG. 14A shows the coupling member 130 aligned for insertioninto the space between two intramedullary stems 200, wherein thedovetailed regions 160 of the coupling member are aligned with thecorresponding dovetailed regions 260 of the stems. The coupling membermay be pushed into the space between the two stems such that thedovetailed regions 160 are engaged within the dovetailed regions 260 ofthe stems. Optionally, the first end 215 of each stem may comprise araised portion with a circumferential opening similarly as in theembodiment of FIGS. 12A-12H, wherein the dovetailed region 260 isdisposed within the rounded cavity defined within the raised portion. Insuch a configuration, the coupling member may be pushed into the spacebetween the two stems until the dovetailed regions 160 hit a hard stopagainst the raised portions of the stems. The coupling member 130 or theintramedullary stem 200 may further comprise one or more turn stops 176,configured to hold the coupling member in place once the coupling memberis coupled to the stem. FIG. 14B shows the assembled delivery system100, wherein each stem 200 comprises a turn stop 176 configured to holdthe coupling member 130. Each turn stop can be rotatable, such that theposition of the turn stop with respect to the stem and the couplingmember can be adjusted. During the step of assembly as shown in FIG.14A, each turn stop may be rotated such that the turn stop does notextend beyond the first end 215 of each stem, thereby allowing thedovetailed region 160 of the coupling member slidingly engage thedovetailed region 260 of the stem without any physical obstruction fromthe turn stop. Once the coupling member is coupled to the stem, the turnstop may be rotated into the position shown in FIG. 14B, such that thelength of the turn stop extends over the junction between the stem andthe coupling member. The turn stop can thus prevent the coupling memberfrom sliding out of engagement with the intramedullary stem.

FIGS. 14C and 14D show a variation of the embodiment shown in FIGS. 14Aand 14B. Instead of turn stops, the coupling member 130 may comprise awinged nut 170, rotatably fixed onto an anterior portion of the couplingmember. The winged nut 170 can be configured to have a length 174 thatis greater than the width 172. The length 174 of the nut can be greaterthan the height 135 of the coupling member. During assembly, thecoupling member 130 may be slidingly inserted into the stems 200 withthe winged nut 170 in the horizontal orientation 173 as shown in FIG.14A. Subsequently, the winged nut 170 may be rotated to so as to be inthe vertical orientation 171 as shown in FIG. 14B, such that the length174 of the nut extends over the junction between the dovetailed regions160 and 260. In the vertical orientation, the winged nut can prevent thecoupling member 130 from sliding out of the stems 200.

Method of Use of Therapeutic Agent Delivery System for Knee

FIG. 15 illustrates a method 1500 of treating a patient's knee using thetherapeutic agent delivery system for a knee as described herein. Instep 1505, a first intramedullary stem is positioned in the medullarycanal of the femur of the patient. In step 1510, a second intramedullarystem is positioned in the medullary canal of the tibia of the patient.In step 1515, the height of an adjustable height manifold is adjusted tofit the joint space between the first stem and the second stem. In step1520, the adjustable height manifold is coupled to the first stem andthe second stem. The adjustable height manifold may be inserted in thejoint space between the first stem and the second stem in a specificorientation appropriate for the connection mechanism used. For example,if the adjustable height manifold comprises stem connections withflanged regions as described herein, configured to engage correspondingrounded cavities of the stems, the adjustable height manifold may beinserted by leading with the two rounded edges of the flanged region. Instep 1525, the coupling between the adjustable height manifold and thefirst and second stems is further secured, via appropriate steps for theconnection mechanism used. For example, if the adjustable heightmanifold comprises the flanged region as described herein, the manifoldmay be rotated to securely engage the flanged region into thecorresponding cavity of the stems. If the adjustable height manifold andthe stems comprise dovetailed regions with turn stops as describedherein, the turn stops may be rotated to extend over the junctionbetween the stem and the manifold, so as to prevent de-coupling of themanifold from the stems. In step 1530, the therapeutic agent isdelivered to the medullary canals of the femur and the tibia and thejoint space.

FIG. 16 illustrates a method 1600 of treating a patient's knee using thetherapeutic agent delivery system for a knee as described herein. Instep 1605, a first intramedullary stem is positioned in the medullarycanal of the femur of the patient. In step 1610, a second intramedullarystem is positioned in the medullary canal of the tibia of the patient.In step 1615, a fixed height wedge with an appropriate height to fit thejoint space between the first stem and the second stem is selected. Instep 1620, the fixed height wedge is coupled to the first stem and thesecond stem, wherein the fixed height wedge may be inserted into thejoint space between the first and second stems in a specific orientationappropriate for the connection mechanism used. For example, if the fixedheight wedge comprises stem connections with flanged regions asdescribed herein, configured to engage corresponding rounded cavities ofthe stems, the fixed height wedge may be inserted by leading with thetwo rounded edges of the flanged region. In step 1625, the couplingbetween the fixed height wedge and the first and second stems is furthersecured, via appropriate steps for the connection mechanism used. Forexample, if the fixed height wedge comprises the flanged region asdescribed herein, the fixed height wedge may be rotated to securelyengage the flanged region into the corresponding cavity of the stems. Ifthe fixed height wedge and the stems comprise dovetailed regions withturn stops as described herein, the turn stops may be rotated to extendover the junction between the stem and the fixed height wedge, so as toprevent de-coupling of the fixed height wedge from the stems. In step1630, the therapeutic agent is delivered to the medullary canals of thefemur and the tibia and the joint space.

The steps of methods 1500 and 1600 are provided as examples of methodsof using a therapeutic agent delivery system in accordance withembodiments. A person of ordinary skill in the art will recognize manyvariations and modifications of methods 1500 and 1600 based on thedisclosure provided herein. For example, some steps may be added orremoved. One or more steps may be performed in a different order than asillustrated in FIGS. 15 and 16. Some of the steps may comprisesub-steps. Many of the steps may be repeated as many times asappropriate or necessary.

Therapeutic Agent Delivery System for Hip

FIGS. 17A and 17B show an exemplary therapeutic agent delivery system500 for a hip. FIG. 17A is a perspective view of the assembled deliverysystem, while FIG. 17B is an exploded perspective view of the system.The delivery system 500 comprises a femoral stem 510 and a femoral head520. The femoral stem 510 can be configured to disposed in a femoralmedullary canal of a patient. The femoral head 520 can be configured tobe disposed in an acetabulum of the patient. The femoral stem maycomprise an inlet 535 configured to couple to a source of a therapeuticagent to be delivered to the patient. The inlet can be fluidly coupledto a channel in the femoral stem, so as to allow the therapeutic agentto be distributed in the femoral medullary canal. The femoral stem andthe femoral head may be configured to removably couple together so as tofluidly connect the femoral stem channel to one or more channels in thefemoral head, such that the therapeutic agent can also be distributed inthe acetabular joint space. The femoral stem and the femoral head may beconfigured to couple in a stable configuration, so as to maintain adesired distance between the femoral stem and the femoral head throughthe length of use of the therapeutic agent delivery system in thepatient. Optionally, the femoral stem and the femoral head may beconnected in a fashion that allows the distance between the stem and thehead to be adjusted to fit the anatomy of the patient. The system 500may further comprise a stem plug 530, configured to couple to an end ofthe femoral stem.

Femoral Stem

FIGS. 18A-18D show an exemplary femoral stem 600 suitable forincorporation with a therapeutic agent delivery system for a hip. FIG.18A is a perspective view, FIG. 18B is a side view, FIG. 18C is a bottomview, and FIG. 18D is a side cross-sectional view of the femoral stem600. The femoral stem 600 comprises an elongate body 605 having alongitudinal axis 610, the elongate body having a first end 615 and asecond end 620 opposite the first end. The elongate body comprises aneck region 650 disposed near the first end 615, wherein the neck regionmay be configured to couple to the femoral head. The second end 620 maybe configured be disposed in the femoral medullary canal. The femoralstem 600 further comprises an inlet 535, configured to be coupled to asource of the therapeutic agent. The inlet 535 is in fluid communicationwith a stem channel 625 extending between the first end 615 and thesecond end 620, as best seen in FIG. 18D. The stem channel can beconfigured to deliver the therapeutic agent through the stem and to themedullary canal. Further, the stem channel can be configured to fluidlycouple to one or more channels in the femoral head.

The elongate body 605 may have one or more structures or features thatare similar to the intramedullary stem 200 described previously. Forexample, the femoral stem 600 may comprise a plurality of protrusions630, protruding radially outward from the elongate body 605. Theplurality of protrusions may comprise any number of protrusions havingany appropriate shape, size, or configuration to engage the medullarycanal in a stable fashion. For example, the protrusions may compriseelongate fins extending along the longitudinal length of the elongatebody, as shown in FIGS. 18A-18D. In one exemplary embodiment, theplurality of protrusions may comprise four fins, spaced equally at about90° about the longitudinal axis 610 of the elongate body. Of course thisis not intended to be limiting, and the number of fins may be anynumber, such as three fins spaced approximately 120 degrees apart, fivefins spaced approximately 72 degrees apart, etc. The plurality ofprotrusions 630 and the elongate body 605 may be formed separately andcoupled together. Alternatively or in combination, the plurality ofprotrusions 630 may be formed by removing material from the elongatebody 605, such that the plurality of protrusions and the elongate bodyare formed as a single member. Adjacent protrusions 630 may define oneor more fluted regions 635 therebetween, the fluted regions radiallyrecessed compared to the protrusions.

The plurality of protrusions and fluted regions can be configured tominimize the surface area of the stem contacting the bone lining themedullary canal, such that the area of the bone flushed with thetherapeutic agent may be maximized. For example, the plurality ofprotrusions and fluted regions can be configured such that less than 50%of the surface area of the stem is in contact with the bone lining themedullary canal. Of course this is not intended to be limiting and oneof skill in the art will appreciate that any percentage of surface areaof the stem may contact the bone. The stem may comprise a plurality ofidentical fluted regions defined by a plurality of elongate fins,distributed symmetrically about the longitudinal axis 610 of the stem,as shown in FIGS. 18A-18D. Alternatively, a plurality of fluted regionsmay be distributed asymmetrically about the longitudinal axis of thestem, and/or may have different shapes or sizes. For example, theelongate body 605 may comprise protrusions and fluted regions asdescribed in relation to FIGS. 3A and 3B.

The femoral stem 600 may further comprise a plurality of outlet holes640 in fluid communication with the stem channel 625. The plurality ofoutlet holes 640 may be configured to deliver the therapeutic agent,distributed through the stem channel 625, to the femoral medullarycanal, as well as adjacent tissue including the joint. The plurality ofoutlet holes may be disposed in a fluted region 635, so as to deliverthe therapeutic agent to the area of the bone not in contact with thefemoral stem. The plurality of outlet holes may comprise any number ofoutlet holes having any appropriate size, shape, or distribution. Forexample, the plurality of outlet holes may include a plurality ofequally sized and spaced holes that extend axially along a linesubstantially parallel to the longitudinal axis 610 of the stem, asshown in FIGS. 18A-18D. Alternatively, the plurality of outlet holes mayextend along a helical or spiral line as shown in FIG. 3A, or the holesmay extend about a plurality of rings around the circumference of theelongate body, as shown in FIG. 3B. The plurality of outlet holes maycomprise holes having an identical shape and/or size, or holes havingvarious shapes and/or sizes. Varying the hole size may allow furtherfluid control of therapeutic agent as it exits different regions of thestem.

The stem channel 625 may be a through hole that extends from the firstend 615 to the second end 620 through both the first end and the secondend, such that the elongate body comprises an open second or distal end.The system may further comprise a plug, shown in FIG. 19, configured tocouple to the open second end of the stem, so as to close the second endand thereby create a blind channel. Alternatively, the stem channel 625may be a blind channel, wherein the second end of the elongate body isclosed. In configurations wherein the second end is open, thetherapeutic agent may exit the stem channel into the medullary canalthrough the second end and/or through a plurality of outlet holesdisposed along the elongate body 605 as described herein. If the stemcomprises only the stem channel 625 extending through the first andsecond ends, without the plurality of outlet holes, the therapeuticagent may exit the stem channel only through the second end. Inconfigurations wherein the second end of the stem is closed, thetherapeutic agent may exit the stem channel into the medullary canalonly through the plurality of outlet holes.

The neck region 650 extends along a neck axis 655, disposed at an angle660 with respect to the longitudinal axis 610 of the elongate body 605.The angle 660 may be in a range from about 120° to about 160°, about130° to about 150°, about 140° to about 150°, or about 145°. The neckregion may comprise one or more connection mechanisms or features tocouple to the femoral head. For example, as shown, the neck region maycomprise a plurality of threads 670, configured to threadably engagecomplementary threads on the femoral head.

The femoral stem 600 may be tapered to fit the medullary canal. Forexample, the elongate body 605 and/or the plurality of protrusions 630may be tapered from the first end 615 to the second end 620, as shown,so as to have a smaller radial cross-sectional area at the second endthan at the first end. For example, the taper may comprise a gradualtaper, wherein the extent of the taper may be in a range from about 0.1°to about 10°, about 0.5° to about 5°, about 1° to about 5°, about 1° toabout 4°, or about 2° or about 3°. The taper may be adjusted toaccommodate a medullary canal of a specific type of bone.

FIG. 19 shows a stem plug 530 suitable for incorporation with anytherapeutic agent delivery system as described herein. The stem plug 530may comprise a smaller diameter region 535 and a larger diameter region540. The smaller diameter region may be configured to be press-fit intoan open second end of an elongate body of any intramedullary stem or hipstem as described herein.

Femoral Head

FIGS. 20A and 20B show an exemplary embodiment of a femoral head 700,suitable for incorporation with a therapeutic agent delivery system fora hip. FIG. 20A is a side view, and FIG. 20B is a side cross-sectionalview of the femoral head 700, along line A-A as shown in FIG. 20A. Thefemoral head 700 can comprise the shape of a truncated sphere, whereinthe truncated base 715 of the head is configured to couple to thefemoral stem. The femoral head 700 comprises a head central channel 725,extending axially along a central axis 710 of the femoral head. Thecentral channel 725 is configured couple to the neck of the femoralstem, and thereby be in fluid communication with the hip stem channelwhen the femoral head is connected to the femoral stem. The femoral headfurther comprises a plurality of outlet holes 740, fluidly coupled tothe central channel 725. The outlet holes may be configured to extendradially outwards from the central channel. Thus, a therapeutic agentmay be supplied to the delivery system via an inlet of the femoral stem,move through the stem channel into the central channel 725 of thefemoral head, and exit into the acetabular joint space through theoutlet holes 740.

The base 715 may comprise one or more mechanisms for coupling thefemoral head to the neck region of the femoral stem. For example, asshown, a portion of the central channel 725 near the base 715 maycomprise a plurality of threads 770, configured to threadably engage aplurality of complementary threads of the femoral stem neck. A threadedconnection between the femoral head and the femoral stem neck can allowthe distance between the femoral head and the femoral stem to beadjusted to fit the patient's anatomy. Optionally, the femoral head maybe further configured to receive one or more set screws near the base,wherein the set screws can fix the distance between the femoral head andthe femoral stem once the distance is appropriately set. For example, asshown in FIG. 20B, the base may comprise two set screw receiving regions780, wherein each set screw receiving region comprises a plurality ofthreads 785 to engage a set screw having complementary threads. The setscrew receiving regions can extend radially outwards from the centralchannel, such that the ends of the set screws can be directly orindirectly coupled to the neck of the femoral stem disposed within thecentral channel. While FIG. 20B shows two set screw receiving regionsradially offset from one another by about 180°, the femoral head maycomprise any number of set screws distributed in any appropriateconfiguration. For example, the femoral head may comprise three setscrew receiving regions radially offset from one another by about 120°,or four set screw receiving regions radially offset from one another byabout 90°.

FIGS. 21A and 21B show another exemplary embodiment of a femoral head800, suitable for incorporation with a therapeutic agent delivery system500 for a hip. The femoral head 800 is partially hollowed, so as toreduce the material mass and weight of the femoral head. The femoralhead 800 comprises a central channel 825, configured to be in fluidcommunication with the stem channel of the femoral stem as describedherein. The femoral head further comprises an inner shell 830 and anouter shell 835, wherein the inner and outer shells are thin, truncatedspherical shells disposed about the periphery of the femoral head. Theinner shell 830 is connected to the material disposed about and definingthe central channel 825. The outer shell 835 is connected to the innershell 830 via a plurality of support struts 845 extending between theinner shell and the outer shell. The inner shell defines an inner cavity855 between the inner shell and the material defining the centralchannel. The inner cavity 855 is hollow, and configured to be sealedagainst the central channel and the inner shell, such that no fluid canenter the inner cavity during use of the delivery system. The innershell and the outer shell define an outer cavity 850 therebetween,wherein the outer cavity 850 is fluidly coupled to the central channel825. The outer shell comprises a plurality of outlet holes 840, suchthat fluid in the outer cavity 850 can exit the femoral head through theoutlet holes. Thus, the therapeutic agent supplied through an inlet of afemoral stem can move through the stem channel into the central channel825 of the femoral head 800, into the outer cavity 850, and through theoutlet holes 840 into the acetabular joint space. Components of thefemoral head 800 may be formed via 3D printing or laser sintering.

FIG. 22 shows another exemplary embodiment of a femoral head 900,suitable for incorporation with a therapeutic agent delivery system fora hip. The femoral head 900 comprises a central channel 925, configuredto be in fluid communication with the stem channel of the femoral stemas described herein. The femoral head further comprises a plurality ofhollow tubes 940 extending radially outwards from the central channel925 and fluidly coupled to the central channel. The femoral head furthercomprises an outer shell 935, a thin, truncated spherical shell disposedabout the periphery of the femoral head. The outer shell 935 is coupledto the plurality of hollow tubes 940, such that the hollow tubes 940extend through the thickness of the outer shell. The hollow tubes, theouter shell, and the material disposed about defining the centralchannel together define a plurality of inner cavities 855, which arehollow and configured to be fluidly sealed, such that no fluid can enterthe inner cavities during use of the delivery system. Thus, thetherapeutic agent supplied through an inlet of a femoral stem can movethrough the stem channel into the central channel 925 of the femoralhead 900, into the plurality of hollow tubes 940, and into theacetabular joint space. The internal diameter of the hollow tubes and/orthe thickness of the hollow tubes may be varied to control the flow offluid within the femoral head, and to adjust the amount of supportprovided by the hollow tubes to the outer shell to protect the integrityof the outer shell.

Coupling Mechanisms

FIGS. 23A and 23B show exemplary mechanisms for coupling a femoral head520 to a femoral stem 510. The femoral head 520 may comprise any femoralhead as described herein, such as femoral heads 700, 800, and 900described in relation to FIGS. 20A-22. The femoral stem 510 may compriseany femoral stem as described herein, such as any embodiment of thefemoral stem 600 described herein. FIG. 23A is a side cross sectionalview of a femoral head 520 coupled fixedly to a femoral stem 510. Theneck region 650 of the stem is fixedly coupled to a portion of thecentral channel 725 of the femoral head, such that the length 540 of theneck that engages the femoral head is fixed. For example, the neck 650may be press-fitted into the central channel 725, such that the neckadvances into the central channel by a pre-determined length. The neck650 may comprise regions having different diameters so as to create anotch between the regions, wherein the notch can provide a stop againstthe femoral head surface when the neck 650 has been advanced into thecentral channel by the pre-determined length. In a delivery systemincorporating such a connection mechanism, the distance between thefemoral head and the femoral stem is fixed. FIG. 23B is a side crosssectional view of a femoral head 520 coupled adjustably to a femoralstem 510. The neck region 650 of the stem is adjustably coupled to aportion of the central channel 725, for example via engagement ofthreads 670 disposed on the neck 650 of the stem with complementarythreads 770 disposed on a portion of the central channel 725. The length540 of the neck that engages the central channel can thereby beincreased or decreased by threadably rotating the femoral head about thefemoral stem. As the femoral head is rotated to axially translate thehead farther away from the femoral stem, the length 540 decreases, andthe distance between the femoral head and the femoral stem increasessuch that the delivery system can be suitable for patients requiring alonger set distance between the femur and the acetabulum. As the femoralhead is rotated to axially translate the head closer to the femoralstem, the length 540 increases, and the distance between the femoralhead and the femoral stem decreases such that the delivery system can besuitable for patients requiring a shorter set distance between the femurand the acetabulum. In a delivery system incorporating such a connectionmechanism, the distance between the femoral head and the femoral stemcan be thus adjusted to accommodate the anatomy of a patient.

FIGS. 24A and 24B show an exemplary mechanism for locking a set distancebetween a femoral head 520 and a femoral stem 510 of a therapeutic agentdelivery system for a hip. The femoral head 520 may comprise any femoralhead as described herein, such as femoral heads 700, 800, and 900described in relation to FIGS. 20A-22. The femoral stem 510 may compriseany femoral stem as described herein, such as any embodiment of thefemoral stem 600 described herein. FIG. 24A is a perspective view andFIG. 24B is a bottom view of a femoral head 520 comprising the exemplarymechanism. As described herein, a femoral head 520 may comprise a pairof set screw receiving regions 780 near the base 715 of the head, whichcan receive a pair of set screws configured to engage the femoral stemneck disposed in the central channel 725 of the femoral head, so as tofix the position of the stem neck therein. The femoral head may furthercomprise a pair of blocks 550 disposed within the set screw receivingregions 780, adjacent to the central channel 725. Each block can becoupled with a set screw 554, wherein the block may comprise a roundedcavity to receive the end of the set screw, and wherein the end of theset screw may be free to rotate within the rounded cavity. Two dowelpins 552 may be coupled to the block-set screw assembly so as to limitthe translational motion of the set screw relative to the block.Rotation of the set screw within the set screw receiving region cancause the block coupled thereto to translate radially inwards oroutwards. The block may be translated radially inwards until the blockengages and pushes against the neck region of the stem disposed withinthe central channel, thereby preventing further rotation of the femoralhead about the femoral stem. The block can distribute the forces betweenthe neck and the set screw across a broader surface, to more effectivelylock the position of the neck. While FIGS. 24A-24F show a pair of setscrew receiving regions radially offset from one another by about 180°,the locking mechanism may comprise any number of set screws distributedin any appropriate configuration. For example, the femoral head maycomprise three set screw receiving regions radially offset from oneanother by about 120°, or four set screw receiving regions radiallyoffset from one another by about 90°.

FIGS. 24C-24F illustrate a method of assembling the locking mechanism ofFIGS. 24A and 24B. FIG. 24C shows the femoral head 520 and components ofthe locking mechanism before assembly. As described previously, thefemoral head may comprise one or more set screw receiving regions 780extending radially outwards from the central channel 725. Each set screwreceiving region can be configured to receive a set screw 554, a block550, and a pair of dowel pins 552. FIG. 24D shows the first step ofassembly of the locking mechanism, wherein the block 550 is coupled tothe femoral head 520. The femoral head may comprise a block receivingregion 556 adjacent the central channel 725, and the block may beinserted into block receiving region from the base 715 of the femoralhead. As best seen in FIG. 24B, the block 550 may have a concave surface551 on a first end and a round indent 553 on a second end opposite thefirst end. As shown in FIG. 24C, the block may be inserted into thefemoral head with the concave surface directed radially inwards, facingthe central channel, and the round indent directed radially outwards.FIG. 24E shows the second step of assembly of the locking mechanism,wherein the set screw 554 is coupled to the femoral head 520. As bestseen in FIG. 24B, the set screw receiving region 780 comprises set screwthreads 785, configured to engage the thread region of the set screw.The set screw may be threadably engaged with the set screw threadswithin the set screw receiving region, to translate the set screwradially inwards within the set screw receiving region. As best seen inFIG. 24D, the set screw can comprise a set screw head 555, an unthreadedregion of the set crew having a smaller diameter than the threadedregion of the set screw. During the step shown in FIG. 24E, the setscrew can be translated radially inwards until the set screw head isdisposed within the round indent 553 of the block 550 (as best seen inFIG. 24B). FIG. 24F shows the final step of assembly of the lockingmechanism, wherein the dowel pins 552 are coupled to the femoral head.The two dowel pins may be pressed into the block 550 with aninterference fit. When the dowel pins are pressed completely into theblock, the leading ends of pins can engage the set screw head 555, suchthat the pins prevent the set screw from separating from the block. Forexample, the screw head may comprise a concave groove 557 (as best seenin FIGS. 24B and 24D) extending about the circumference of the set screwhead 555. The leading ends of the dowel pins may be configured to engagethe concave groove when the pins are pressed completely into the block(as best seen in FIG. 24B) such that the set screw cannot separate fromthe block.

Optional Features

FIGS. 25A and 25B show an exemplary embodiment of a therapeutic agentdelivery system 500 for a hip, further comprising an acetabular cup 560.FIG. 25A is a perspective view and FIG. 25B is a side cross sectionalview of the system 500. The delivery system 500 may further comprise aseparate acetabular cup 560, configured to be inserted into theacetabular space of the hip joint. The femoral head 520 thus interfaceswith the acetabular cup, rather than interfacing directly with theacetabulum of the patient. The acetabular cup may comprise a pluralityof fluted external structures 565, through which fluid may flow to reachthe acetabulum.

FIG. 26 shows an exemplary embodiment of a therapeutic agent deliverysystem 500 for a hip. The therapeutic agent delivery system 500 asdescribed herein may be configured to function as the final implant,rather than as a temporary implant intended for the first stage of atwo-stage re-implantation procedure. The system 500 may comprise afemoral stem 510 such as any femoral stem described herein, a femoralhead 520 such as any femoral head described herein, and a stem plug 530.In addition, the system 500 may further comprise a liner 570 and anacetabular cup 560 configured to be implanted between the femoral head520 and the acetabulum of the patient. Fluid may flow through thefemoral head and out the liner and acetabular cup, into the joint spaceand the acetabulum. Optionally, alternatively to or in combination withthe inlet 535 of the femoral stem 510, the acetabular cup 560 maycomprise a separate inlet, through which the therapeutic agent may besupplied.

Method of Use of Therapeutic Agent Delivery System for Hip

FIG. 27 illustrates a method 1700 of treating a patient's hip using atherapeutic agent delivery system for a hip as described herein. In step1705, a femoral stem is positioned in the medullary canal of thepatient's femur. In step 1710, a femoral head is coupled to the femoralstem. In step 1715, which is optional, the distance between the femoralstem and the femoral head is adjusted such that the delivery system bestfits the patient's anatomy. For example, if the femoral head is coupledto the femoral stem via a threaded connection mechanism as describedherein, the distance between the femoral stem and head may be adjustedby threadably rotating the femoral head about the stem. Step 1715 mayfurther comprise locking the distance between the femoral head and thefemoral stem, for example via the set screw mechanism described inrelation to FIGS. 24A-24F. In step 1720, the femoral head is positionedin the patient's acetabulum. In step 1725, the therapeutic agent isdelivered to the medullary canal and the acetabulum via the deliverysystem.

The steps of method 1700 are provided as examples of a method of using atherapeutic agent delivery system in accordance with embodiments. Aperson of ordinary skill in the art will recognize many variations andmodifications of the method 1700 based on the disclosure providedherein. For example, some steps may be added or removed. Some of thesteps may comprise sub-steps. Many of the steps may be repeated as manytimes as appropriate or necessary. One or more steps may be performed ina different order than as illustrated in FIG. 27. For example, thefemoral head and the femoral stem may be coupled together and, ifnecessary, the distance between the head and stem adjusted, before theassembled device is positioned in the patient's femur and acetabulum.

Additional Features of Therapeutic Agent Delivery Systems

In any of the therapeutic agent delivery systems described herein, theflow of fluid within the system may be adjusted by modifying one or moredimensions or configurations of the channels and/or outlet holes. Forexample, the diameter of the channels and/or outlet holes may beincreased or decreased, or channels may be configured to have varyingdiameters along the length of the assembly, to bias the flow of fluid ina particular direction. Angles at junctures between the channels mayalso be varied to bias fluid flow within the system.

Any therapeutic agent delivery system as described herein may furthercomprise a pump, operatively coupled to the inlet. The pump may beconfigured to pump the therapeutic agent into one or more channels ofthe system.

Any therapeutic agent delivery system as described herein may optionallycomprise a vacuum pump that may be coupled to an inlet or an outlet ofthe system. The vacuum pump may be configured to remove any unwanted orexcess fluids from the body of the patient, before introducing thetherapeutic agent to the body using the delivery system.

Any therapeutic agent delivery system as described herein may optionallycomprise a port under the skin that is coupled to an inlet or outlet ofthe delivery system. The port may be accessed via a needle or syringe asnecessary.

FIGS. 28A and 28B illustrate the use of negative pressure wound therapywith a therapeutic agent delivery system for a knee. Negative pressurewound therapy may optionally be used in tandem with the therapeuticagent delivery system, in order to further improve the prognosis of thetreatment. The wound of the patient can be packed with sponges 90 andoptionally covered with a wound dressing 85 coupled to a vacuum pump 80.Actuation of the vacuum pump can then draw blood and nutrients toinfected areas. As shown in FIG. 28B, optional sponges for negativepressure wound therapy may also be provided as strips 95 of spongesconfigured to be disposed along the intramedullary stems 200 of thedelivery system 100. The strips of sponges may be trimmed to fit thespace along the fluted regions 235 of any intramedullary stem 200.Negative pressure wound therapy can pull material through the sponge andinto the plurality of outlet holes of the stem, into the stem channel,and out of the body through the inlet or outlet of the system. While adelivery system for a knee is shown in FIGS. 28A and 28B, negativepressure wound therapy may be used with any therapeutic agent deliverysystem as described herein, including delivery systems for joints otherthan the knee.

FIG. 29 shows an optional cover 75 for an intramedullary stem 200,suitable for incorporation with any therapeutic agent delivery systemdescribed herein. The cover 75 may comprise a thin, cone-shaped sponge,configured to fit inside the medullary canal as an interface between thebone and the intramedullary stem 200. The cover can be configured tocover the substantially all of the elongate body 205 of the stem, andthus evenly interface with the intramedullary bone. When covered withthe cover 75, the therapeutic agent can disperse within the cover andreach the corresponding surface of the medullary canal, regardless ofthe shape of the intramedullary stem (e.g., shape, size, number, orconfiguration of protrusions and fluted regions). This exemplaryconfiguration may also be used in conjunction with the negative pressurewound therapy previously described.

FIG. 30 shows an exemplary embodiment of a therapeutic agent deliverysystem 1000. The delivery system 1000 may comprise an intramedullarystem 1010 which may be any intramedullary stem as described herein, suchas intramedullary stems 110, 120, or 200, or femoral stems 510 or 600.The stem 1010 may comprise a stem channel 1025 that extends through boththe first end 1015 and the second end 1020 of the stem. Instead ofreceiving the therapeutic agent from a coupling member coupled to thestem, the stem 1010 may be configured to receive a catheter 1030supplying the therapeutic agent through the first end 1015. Thetherapeutic agent may be delivered to the medullary canal through thesecond end 1020.

FIGS. 31A and 31B show exemplary embodiments of therapeutic agentdelivery systems with inlets and outlets. FIG. 31A shows an exemplaryembodiment of a therapeutic agent delivery system 100 for a knee, asdescribed herein. The delivery system 100 may comprise an inlet 140,configured to couple to a source of the therapeutic agent. The inlet 140may be fluidly coupled to one or more channels of a coupling member 130,and the one or more channels of the coupling member may be fluidlycoupled to the stem channels in the stems 200. Optionally, the systemmay further comprise an outlet 145, configured to remove the therapeuticagent and/or any other fluid from the body. The stems and the couplingmember may comprise internal channels configured to direct fluid betweenthe inlet and the stem channel, and between the stem channel and theoutlet. Other aspects of the system may generally take the same form aspreviously described. FIG. 31B shows an exemplary embodiment of atherapeutic agent delivery system 500 for a hip, as described herein.The delivery system 500 may comprise an inlet 535, configured to coupleto a source of the therapeutic agent. The inlet 535 may be fluidlycoupled to a channel of the femoral stem 510, and the stem channel maybe fluidly coupled to a central channel of the femoral head 520 coupledto the femoral stem. Optionally, the system may further comprise anoutlet 545, configured to remove the therapeutic agent and/or any otherfluid from the body. The femoral stem and the femoral head may compriseinternal channels configured to direct fluid between the inlet and thechannels of the stem and the head, and between the outlet and thechannels of the stem and the head. Other aspects of the system maygenerally take the same form as previously described.

FIGS. 32A and 32B illustrate an exemplary configuration for the internalchannels of an intramedullary stem. FIG. 32A is a sectional view andFIG. 32B is a cross sectional view of an intramedullary stem 1100comprising a plurality of separate internal fluid paths. Stem 1100 maycomprise any intramedullary stem as described herein, such asintramedullary stems 110, 120, or 200, or femoral stems 510 or 600. Stem1100 may comprise a first internal channel 1110 centrally disposed alongthe longitudinal axis of the stem, and a second internal channel 1120disposed about the periphery of the first internal channel (the secondinternal channel can form the shape of a cylindrical shell surroundingthe first internal channel). The first internal channel may be fluidlycoupled to a first plurality of outlet holes 1115, each of the firstplurality of outlet holes extending from the first internal channel,through the second internal channel, to an outer wall of the stem (suchas a fluted region 1135 of the stem). The second internal channel may befluidly coupled to a second plurality of outlet holes 1125, each of thesecond plurality of outlet holes extending from the second internalchannel directly to an outer wall of the stem. The first internalchannel and the second internal channel may be fluidly sealed againstone another, and each of the first plurality of outlet holes 1115 maycross over the second internal channel 1120 through a side channel thatis fluidly sealed against the second internal channel. Therefore, thefirst internal channel and the second internal channel can form twoseparate internal fluid paths, each of which can be used to deliverfluid to the tissue or remove fluid from the tissue. As shown in FIG.32B, the first plurality of outlet holes 1115 and the second pluralityof outlet holes 1125 may be linearly arranged along the length of thestem in an alternating manner, such that every other hole is in fluidcommunication with a different internal fluid path.

FIGS. 33A-33C illustrate another exemplary configuration for theinternal channels of an intramedullary stem. FIG. 33A is a perspectiveview, FIG. 33B is a vertical cross sectional view, and FIG. 33C is ahorizontal cross sectional view of an intramedullary stem 1200comprising a plurality of separate internal fluid paths. Stem 1200 maycomprise any intramedullary stem as described herein, such asintramedullary stems 110, 120, or 200, or femoral stems 510 or 600. Stem1200 may comprise a first internal channel 1210 running along the lengthof the stem, and a second internal channel 1220 adjacent the firstinternal channel, also running along the length of the stem. The firstand second internal channels may be fluidly sealed against one another,such that each channel forms a separate internal fluid path. The firstinternal channel may be fluidly coupled to a first plurality of outletholes 1215, each of the first plurality of outlet holes extending fromthe first internal channel to an outer wall of the stem (such as a fluidregion 1235 of the stem), without cutting through the second internalchannel. The second internal channel may be fluidly coupled to a secondplurality of outlet holes 1225, each of the second plurality of outletholes extending from the second internal channel to an outer wall of thestem, without cutting through the first internal channel. Therefore, thefirst internal channel and the second internal channel can form twoseparate internal fluid paths, each of which can be used to deliverfluid to the tissue or remove fluid from the tissue. As shown in FIG.33A, the first plurality of outlet holes 1215 and the second pluralityof outlet holes 1225 may be arranged along the length of the stem in analternating manner, such that every other hole is in fluid communicationwith a different internal fluid path.

An intramedullary stem comprising two or more separate internal fluidpaths as shown in FIGS. 32A-33C may be used to simultaneously deliverfluid to and remove fluid from the tissue, without cross-contaminatingthe fluid to be delivered with the fluid to be removed. For example, afirst internal channel may be fluidly coupled to an inlet (such as inlet140 of FIG. 31A or inlet 535 of FIG. 31B) configured to receive atherapeutic agent from a source, while the second internal channel maybe fluidly coupled to an outlet (such as outlet 145 of FIG. 31A oroutlet 545 of FIG. 31B) configured to remove fluid from the tissue. Inthis configuration, the first plurality of outlet holes can deliver thetherapeutic agent to the tissue, while the second plurality of outletholes can remove fluid from the tissue, thereby allowing simultaneousdelivery of therapeutic agent and removal of fluid from the tissuewithout cross-contamination between the therapeutic agent and the fluidto be removed. In another exemplary configuration, the first internalchannel may be fluidly coupled to a first inlet configured to receive afirst therapeutic agent, while the second internal channel may befluidly coupled to a second inlet configured to receive a secondtherapeutic agent different from the first therapeutic agent. In thisconfiguration, simultaneous delivery of two different therapeutic agentscan be achieved, without cross-contamination between the two agentsbefore the agents reach the tissue.

FIGS. 34-36 show exemplary embodiments of therapeutic agent deliverysystems adapted for use in various joints. While descriptions of thetherapeutic agent delivery systems are primarily directed to systems tobe used in the knee or in the hip, systems comprising similar componentsand features may be used to treat any other joint. FIG. 34 shows anexemplary embodiment of a delivery system 1200 for a shoulder, FIG. 35shows an exemplary embodiment of a delivery system 1300 for an ankle,and FIG. 36 shows an exemplary embodiment of a delivery system 1400 fora spine. In the embodiments shown, the delivery systems 1200, 1300, and1400 comprise an inlet 140 through which the therapeutic agent may besupplied, and a plurality of outlet holes 240 through which thetherapeutic agent may be delivered to the respective location of thebody. Any of the delivery systems 1200, 1300, and 1400 may incorporateany other structures or features disclosed herein in relation todelivery systems for the knee and the hip.

Components of the therapeutic agent delivery systems as described hereinmay be formed from one or more of many materials commonly used inorthopedic implants, including but not limited to titanium alloy Ti6A1-4V, polyether ether ketone (PEEK), polymethyl methacrylate (PMMA),and ultra high molecular weight polyethylene (UHMWPE). The materials mayincorporated an antibiotic-impregnated outer layer, such as anantibiotic-impregnated PMMA outer layer. The surface of the componentsmay be polished to prevent bone growth and formation of biofilms.Alternatively, the surface of the components may be grit-blasted orplasma-sprayed, incorporate one or more of an hyaluronic acid (HA)coating, silver coating, or antibiotic carrier coating, or be passivatedand irradiated to form a hydrophilic nanostructure. The delivery systemsas described herein may comprise one or more of machined parts orsintered parts.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. It is intended thatthe following claims define the scope of the invention and that methodsand structures within the scope of these claims and their equivalents becovered thereby.

What is claimed is:
 1. A therapeutic agent delivery system, said systemcomprising: a first intramedullary stem configured to be disposed in afirst medullary canal of a first bone, the first stem comprising: anelongate body having a longitudinal axis, a first end, a second endopposite the first end, and a channel extending between the first endand the second end; a plurality of protrusions extending radiallyoutward from the elongate body, wherein adjacent protrusions define oneor more fluted regions therebetween, and wherein the plurality ofprotrusions are configured to engage the first medullary canal in astable fashion, and wherein one or more outlet holes are disposed in theone or more fluted regions, the one or more outlet holes in fluidcommunication with the channel; a second intramedullary stem configuredto be disposed in a second medullary canal of a second bone, the secondstem comprising: an elongate body having a longitudinal axis, a firstend, a second end opposite the first end, and a channel extendingbetween the first end and the second end; a plurality of protrusionsextending radially outward from the elongate body, wherein adjacentprotrusions define one or more fluted regions therebetween, and whereinthe plurality of protrusions are configured to engage the firstmedullary canal in a stable fashion, and wherein one or more outletholes are disposed in the one or more fluted regions, the one or moreoutlet holes in fluid communication with the channel; and a couplingmember coupled to the first end of the first intramedullary stem and thefirst end of the second intramedullary stem, wherein the coupling memberholds the first intramedullary stem and the second intramedullary stemtogether and at a fixed distance, and wherein the coupling memberfurther comprising an inlet in fluid communication with the channels inthe first and second intramedullary stems.
 2. The system of claim 1,wherein the coupling member comprises an adjustable height manifoldconfigured to increase or decrease a distance between the first ends ofthe two intramedullary stems when the adjustable height manifold isactuated.
 3. The system of claim 2, wherein the adjustable heightmanifold comprises a housing with a central housing channel disposedtherethrough, a rotating nut coupled to the housing, and an adjustableconnector disposed in the housing channel, the adjustable connectorhaving an adjustable connector channel disposed therein, wherein theinlet, coupled to the housing, is fluidly coupled to the adjustableconnector channel, and the adjustable connector channel is fluidlycoupled to the channel in the first or second stem, and wherein rotationof the rotating nut extends or retracts the adjustable connectorrelative to the housing.
 4. The system of claim 3, wherein the rotatingnut is threadably engaged with the adjustable connector, and wherein theadjustable connector is slidably disposed in the housing channel, andwherein rotation of the rotating nut moves the adjustable connector upor down in the housing channel without rotation of the adjustableconnector.
 5. The system of claim 1, wherein the coupling membercomprises a wedge element, wherein disposition of the wedge elementbetween the first end of the first intramedullary stem and the first endof the second medullary stem adjusts a distance between the first endsof the two intramedullary stems.
 6. The system of claim 1, furthercomprising a source of the therapeutic agent for delivery to themedullary canals from the one or more outlet holes in the one or morefluted regions of the first and second stems.
 7. The system of claim 1,wherein the therapeutic agent is an antibiotic.
 8. The system of claim7, wherein the antibiotic comprises vancomycin, tobramycin, or acombination thereof.
 9. The system of claim 1, wherein the firstmedullary canal is in a femur and the first stem is configured to bedisposed therein, and wherein the second medullary canal is in a tibiaand the second stem is configured to be disposed therein.
 10. The systemof claim 1, wherein the coupling member is releasably coupled to thefirst and second intramedullary stems.
 11. The system of claim 1,wherein the first stem is identical to the second stem.
 12. The systemof claim 1, wherein the first stem or the second stem comprises fourfins equally spaced around the elongate body and extending along thelongitudinal axis thereof.
 13. The system of claim 1, wherein the firststem or the second stem comprises a plurality of outlet holes extendingaxially along a line substantially parallel to the longitudinal axisthereof.
 14. The system of claim 1, wherein the coupling membercomprises a flanged region, and wherein the first end of the first orsecond stem comprises a recessed region for receiving the flangedregion, and wherein rotation of the flanged region relative to therecessed region releasably locks the first end with the coupling member.15. The system of claim 14, wherein one or more pins are disposed in thefirst end of the first or second stem, and wherein the one or more pinsprotrude therefrom thereby engaging the flanged region and preventingfurther rotation of the first or second stem relative to the couplingmember.
 16. The system of claim 1, wherein the coupling member comprisesa snap fit section or a dovetailed section for engaging a correspondingdovetailed section or a corresponding snap fit section on the first stemor the second stem.
 17. The system of claim 1, wherein the channelextends from the first end to the second end of the first or secondstem, and wherein the channel extends through both the first end and thesecond end.
 18. The system of claim 17, further comprising a plugdisposed in the channel at the second end of the first stem or thesecond stem.
 19. The system of claim 1, wherein the channel is a blindchannel in the first stem or the second stem, the blind channel having aclosed second end.
 20. The system of claim 1, wherein the elongate bodyof the first stem or the second stem is tapered.
 21. The system of claim1, wherein the coupling member comprises a housing and a first stemconnector configured to engage the first end of the first intramedullarystem and a second stem connector configured to engage the first end ofthe second intramedullary stem, the first and second stem connectorsdisposed on opposite sides of the housing, the first stem connectorhaving an orientation relative to the second stem connector, and whereinthe orientation remains the same during actuation of the adjustableheight manifold.
 22. The system of claim 1, wherein the coupling membercomprises a housing, and wherein a concave groove is disposedcircumferentially around at least a portion of the housing, the concavegroove sized to receive a tubing.
 23. The system of claim 1, furthercomprising a cover disposed over the first stem or the second stem, or asponge disposed in at least some of the one or more fluted regions ofthe first stem or the second stem, and wherein the cover or the spongeis configured to facilitate even distribution of the therapeutic agenttherefrom to the first or the second intramedullary canal.
 24. Thesystem of claim 1, further comprising a pump configured to pump thetherapeutic agent into the channel of the first or the second stem. 25.The system of claim 1, further comprising a vacuum pump, the vacuum pumpconfigured to remove unwanted fluids from the first or the secondmedullary canal via the one or more outlet holes or the channel in thefirst stem or the second stem.
 26. The system of claim 1, wherein theplurality of protrusions in the first stem or the second stem arespirally disposed therearound, or wherein the one or more fluted regionsin the first stem or the second stem are spirally disposed therearound.27. The system of claim 1, wherein the first stem or the second stemhave a surface area, and wherein 50% or less of the surface area isconfigured to contact bone in the first medullary canal or the secondmedullary canal.
 28. The system of claim 1, further comprising an outletfluidly coupled to the first stem, the second stem, or the couplingmember.
 29. A method for treating a joint, said method comprising:positioning a first intramedullary stem in a first medullary canal of afirst bone; positioning a second intramedullary stem in a secondmedullary canal of a second bone; coupling the first intramedullary stemto the second intramedullary stem with a coupling member therebetween;and delivering a therapeutic agent to the first and second medullarycanals.
 30. The method of claim 29, wherein the coupling membercomprises an adjustable height manifold, and wherein the method furthercomprises actuating the adjustable height manifold, thereby adjusting adistance between a first end of the first intramedullary stem and afirst end of the second intramedullary stem.
 31. The method of claim 30,wherein actuating the adjustable height manifold comprises rotating anut coupled to a housing of the adjustable height manifold, and whereinrotating the nut moves an adjustable connector of the adjustable heightmanifold relative to the housing.
 32. The method of claim 29, whereinthe coupling member comprises a wedge element having a fixed height, andwherein the method further comprises selecting a wedge element from aplurality of wedge elements having different fixed heights, and whereincoupling comprises coupling the first intramedullary stem to the secondintramedullary stem with the selected wedge element therebetween,thereby adjusting a distance between a first end of the firstintramedullary stem and a first end of the second intramedullary stem.33. The method of claim 29, wherein positioning the first intramedullarystem in the first medullary canal or positioning the secondintramedullary stem in the second medullary canal comprises engaging aplurality of protrusions on the first or second stem with bone liningthe respective first or second medullary canal.
 34. The method of claim29, wherein delivering the therapeutic agent comprises delivering anantibiotic.
 35. The method of claim 34, wherein the antibiotic comprisesvancomycin, tobramycin, or a combination thereof.
 36. The method ofclaim 29, wherein delivering the therapeutic agent comprises deliveringthe therapeutic agent from one or more outlet holes disposed in a flutedregion of the first stem or the second stem.
 37. The method of claim 29,wherein the first bone is a femur and the second bone is a tibia. 38.The method of claim 29, wherein coupling comprises engaging a flangedregion in the adjustable height manifold with a recessed region in thefirst end of the first stem or the second stem.
 39. The method of claim29, wherein delivering the therapeutic agent comprises pumping thetherapeutic agent from the first stem or the second stem to therespective first or second medullary canal.
 40. The method of claim 29,further comprising suctioning unwanted fluids from the first or thesecond medullary canal, wherein the unwanted fluids pass through one ormore holes in the first stem or the second stem.
 41. The method of claim29, wherein positioning the first stem or the second stem comprisespositioning the first stem or the second stem in the respectivemedullary canal such that 50% or less of a surface area of the firststem or the second stem contacts bone in the respective first or secondmedullar canal.
 42. A therapeutic agent delivery system, said systemcomprising: a femoral head configured to be disposed in an acetabulum; afemoral stem coupled to the femoral head, the femoral stem configured tobe disposed in a femoral medullary canal; an inlet coupled to thefemoral stem; and a plurality of outlets in the femoral head or thefemoral stem, wherein the therapeutic agent is introduced into thesystem from the inlet, and wherein the therapeutic agent is deliverablefrom the plurality of outlets into the acetabulum or the femoralmedullary canal.
 43. The system of claim 42, wherein the femoral stemcomprises a threaded neck region, the threaded neck region configured tobe threadably engaged with the femoral head thereby allowing adjustmentof a distance between the femoral head and the femoral stem.
 44. Thesystem of claim 42, wherein the femoral stem comprises a plurality ofprotrusions extending axially along a longitudinal axis of the femoralstem.
 45. The system of claim 42, wherein the femoral stem comprises anelongate channel extending therethrough, the channel fluidly coupledwith the inlet and the plurality of outlets.
 46. The system of claim 45,wherein the elongate channel is a through hole, and wherein one end ofthe femoral stem comprises a plug.
 47. The system of claim 42, whereinthe femoral stem is tapered.
 48. The system of claim 42, wherein theplurality of outlets are disposed in the femoral head, and wherein thefemoral head comprises a central channel, the central channel fluidlycoupled with the plurality of outlets via a plurality of channelsextending radially outward from the central channel.
 49. The system ofclaim 42, further comprising an outlet for fluid removal from thefemoral head or the femoral stem.
 50. The system of claim 42, furthercomprising an acetabular cup coupled to the femoral head, and whereinthe therapeutic agent is delivered from the acetabular cup to theacetabulum.
 51. The system of claim 42, wherein the plurality of outletscomprise a plurality of holes having varying diameters.
 52. The systemof claim 42, wherein the femoral head is at least partially hollow. 53.The system of claim 42, further comprising a locking mechanism forlocking the femoral head with the femoral stem.
 54. A method fortreating a joint, said method comprising: positioning a femoral stem ina medullary canal of a femur; coupling a femoral head with the femoralstem; positioning the femoral head in an acetabulum; and delivering atherapeutic agent to the medullary canal and the acetabulum.
 55. Themethod of claim 54, wherein coupling comprises adjusting a distancebetween the femoral head and the femoral head.
 56. The method of claim54, wherein coupling comprises threadably engaging the femoral head withthe femoral stem.
 57. The method of claim 54, wherein positioning thefemoral stem comprises engaging a plurality of protrusions on thefemoral stem with bone lining the medullary canal.
 58. The method ofclaim 54, wherein delivering the therapeutic agent comprises deliveringan antibiotic.
 59. The method of claim 58, wherein the antibioticcomprises vancomycin, tobramycin, or a combination thereof.
 60. Themethod of claim 54, wherein delivering the therapeutic agent comprisesdelivering the therapeutic agent from one or more outlet holes disposedin a fluted region of the femoral stem.
 61. The method of claim 54,wherein delivering the therapeutic agent comprises pumping thetherapeutic agent from the femoral stem to the medullary canal or fromthe femoral head to the acetabulum.
 62. The method of claim 54, furthercomprising suctioning unwanted fluids from the medullary canal or theacetabulum.
 63. The method of claim 54, wherein positioning the femoralstem comprises positioning the femoral stem into the medullary canalsuch that 50% or less of a surface area of the femoral stem contactsbone in the medullary canal.
 64. A device for delivering a therapeuticagent to a joint in a patient, said device comprising: an implant havinga plurality of outlets for delivering the therapeutic agent to thejoint, wherein the joint is a shoulder joint, an ankle joint, or aspinal joint.